Skip to main content

Advertisement

SpringerLink
Log in

Correlation study of antibacterial activity and spectrum of Penicillins through a structure-activity relationship analysis

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Penicillins are a group of antibiotics of the beta-lactam group, widely used worldwide as first-choice drugs in the treatment of infections caused by sensitive bacteria. Their use is based on an empirical measure of their activity through antibiograms. In this work we have carried out a structure-activity relationship analysis to elucidate the molecular and physicochemical bases that determine the antibacterial activity and the orientation of the antibacterial spectrum of penicillins, employing a set of bacteria that cause common infections. It was found that the antibacterial activity increases as penicillin size increases for both, Gram-negative and Gram-positive bacteria. In the same way, liposolubility affects the activity; water soluble penicillins have greater activity on Gram-negative bacteria, while in some cases liposoluble penicillins present higher activity against Gram-positive bacteria. In addition, it is proposed that electronic properties of the substituent of the penicillin core determine its antibacterial spectrum. The electron donating substituents make the penicillin active against Gram-positive bacteria, while the electron withdrawing substituents gear the activity towards Gram-negative bacteria. In addition, the alpha-carbon (Cα) of the carboxamide side chain is also essential for the activity against Gram-negative bacteria; penicillins that lack it, have higher activity against Gram-positive bacteria.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12
Fig. 13
Fig. 14
Fig. 15
Fig. 16
Fig. 17
Fig. 18

Similar content being viewed by others

References

  • ACD/ChemSketch, Advanced Chemistry Development, Inc., Toronto, On, Canada, www.acdlabs.com. 2015

  • Adhikari R, Dutt-Pant N, Neupane S, Neupane M, Bhattarai R, Bhatta S, Chaudhary R, Lekhak B (2017) Detection of methicillin resistant Staphylococcus aureus and determination of minimum inhibitory concentration of vancomycin for Staphylococcus aureus isolated from pus/wound swab samples of the patients attending a tertiary care hospital in Kathmandu, Nepal. Can J Infect Dis Med Microbiol 2017:1–6

    Article  CAS  Google Scholar 

  • Alcaide F, Liñares J, Pallares R, Carratala J, Benitez MA, Gudiol F, Martin R (1995) In vitro activities of 22 beta-lactam antibiotics against penicillin-resistant and penicillin-susceptible viridans group streptococci isolated from blood. Antimicrob Agents Chemother 39(10):2243–2247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alpuche ACM, Amaya-Burns A, Andrus JK, Aranda TE, Arathoon E, Arbo SA, Badaró R, Báez E, Basualdo W, Benguigui Y, Bologna R, Camba de Hernández I, Carter K, Castro J, Cimerman S, Clara L, Comegna M, Correa A, Cruz JR, Douce R, Graybaill R, Grazioso C, Gotuzzo E, Gusmao R, Guzmán BM, Heitmann I, Lerner SJ, Martin M, Mejía C, Paredes P, Pleités EB, Rocha MC, Rodríguez R, Salvatierra-González R, Schmuñis GA, Suárez CE, Zurita J (2004) Guía para el tratamiento de las enfermedades infecciosas. Organización Panamericana de la Salud: Oficina Regional de la Organización Mundial de la Salud. 1-294, Washington DC, USA

    Google Scholar 

  • Álvarez S, Jones M, Berk SL (1985) In vitro activity of fosfomycin, alone and in combination, against methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 28(5):689–690

    Article  PubMed  PubMed Central  Google Scholar 

  • Andrews JM (2001) Determination of minimum inhibitory concentrations. J Antimicrob Chemother 49(6):1–16

    Google Scholar 

  • Arlet G, Rouveau M, Fournier G, Lagrange PH, Philippon A (1993) Novel, plasmid-encoded, TEM-derived extended-spectrum beta-lactamase in Klebsiella pneumoniae conferring higher resistance to aztreonam than to extended-spectrum cephalosporins. Antimicrob Agents Chemother 37(9):2020–2023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aubert G, Guichard D, Vedel G (1996) In-vitro activity of cephalosporins alone and combined with sulbactam against various strains of Acinetobacter baumannii with different antibiotic resistance profiles. J Antimicrob Chemother 37(1):155–160

    Article  CAS  PubMed  Google Scholar 

  • Ayers LW, Jones RN, Barry AL, Thornsberry C, Fuchs PC, Gavan TL, Gerlach EH, Sommers HM (1982) Cefotetan, a new cephamycin: comparison of in vitro antimicrobial activity with other cephems, beta-lactamase stability, and preliminary recommendations for disk diffusion testing. Antimicrob Agents Chemother 22(5):859–877

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baker P, Slots J, Genco R, Evans R (1983) Minimal inhibitory concentrations of various antimicrobial agents for human oral anaerobic bacteria. Antimicrob Agents Chemother 24(3):420–424

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baker CN, Thornsberry C (1974) Antimicrobial susceptibility of Streptococcus mutans isolated from patients with endocarditis. Antimicrob Agents Chemother 5(3):268–271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bornside GH (1968) Synergistic antibacterial activity of ampicillin-cloxacillin mixtures against Proteus morganii. J Appl Microbiol 16(10):1507–1511

    CAS  Google Scholar 

  • Bou G, Oliver A, Martínez J (2000) OXA-24, a novel class D β-lactamase with carbapenemase activity in an Acinetobacter baumannii clinical strain. Antimicrob Agents Chemother 44(6):1556–1561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown A, Butterwoth D, Cole M, Hanscomb G, Hood J, Reading C, Rolinson G (1976) Naturally-occurring β-lactamase inhibitors with antibacterial activity. J Antibiot 29(6):668–669

    Article  CAS  PubMed  Google Scholar 

  • Brown S, Young HK, Amyes SG (2005) Characterization of OXA-51, a novel class D carbapenemase found in genetically unrelated clinical strains of Acinetobacter baumannii from Argentina. Clin Microbiol Infect 11(1):15–23

    Article  CAS  PubMed  Google Scholar 

  • Brunton L, Hilal-Dandan R, Knollmann BC (2019) Goodman & Gilman: Las bases farmacológicas de la terapéutica. McGraw-Hill, Mexico, p 960

    Google Scholar 

  • Cai JC, Zhou HW, Zhang R, Chen G-X (2008) Emergence of Serratia marcescens, Klebsiella pneumoniae, and Escherichia coli isolates possessing the plasmid-mediated carbapenem-hydrolyzing β-lactamase kpc-2 in intensive care units of a chinese hospital. Antimicrob Agents Chemother 52(6):2014–2018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chartrand SA, Scribner RK, Weber AH, Welch DF, Marks MI (1983) In vitro activity of CI-919 (AT-2266), an oral antipseudomonal compound. Antimicrob Agents Chemother 23(5):658–663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chin NX, Neu HC (1983) In vitro activity of enoxacin, a quinolone carboxylic acid, compared with those of norfloxacin, new beta-lactams, aminoglycosides, and trimethoprim. Antimicrob Agents Chemother 24(5):754–763

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crosgrove SE, Sakoulas G, Perencevich EN, Schwaber MJ, Karchmer AW, Carmeli Y (2003) Comparison of mortality associated with methicillin-resistant and methicillin-susceptible Staphylococcus aureus bacteremia: a meta-analysis. Clin Infect Dis 36:53–59

    Article  Google Scholar 

  • Da Silva G, Leitao R, Peixe L (1999) Emergence of carbapenem-hydrolyzing enzymes in Acinetobacter baumannii clinical isolates. J Clin Microbiol 37(6):2109–2110

    PubMed  PubMed Central  Google Scholar 

  • Deshpande LM, Jones RN (2003) Bactericidal activity and synergy studies of BAL9141, a novel pyrrolidinone-3-ylidenemethyl cephem, tested against streptococci, enterococci and methicillin-resistant staphylococci. Clin Microbiol Infect 9(11):1120–1124

    Article  CAS  PubMed  Google Scholar 

  • Doern GV, Brueggemann A, Holley HP, Rauch AM (1996) Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients in the United States during the winter months of 1994 to 1995: results of a 30-center national surveillance study. Antimicrob Agents Chemother 40(5):1208–1213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doern GV, Brueggemann AB, Huynh H, Wingert E, Rhomberg P (1999) Antimicrobial resistance with Streptococcus pneumoniae in the United States, 1997–98. Emerg Infect Dis 5(6):757–765

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doern GV, Pfaller MA, Kugler K, Freeman J, Jones RN (1998) Prevalence of antimicrobial resistance among respiratory tract isolates of Streptococcus pneumoniae in North America: 1997 results from the SENTRY antimicrobial surveillance program. Clin Infect Dis 27(4):764–770

    Article  CAS  PubMed  Google Scholar 

  • Dowson CG, Johnson AP, Cercenado E, George RC (1994) Genetics of oxacillin resistance in clinical isolates of Streptococcus pneumoniae that are oxacillin resistant and penicillin susceptible. Antimicrob Agents Chemother 38(1):49–53

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eftekhar F, Raei F (2011) Correlation of minimum inhibitory concentration breakpoints and methicillin resistance gene carriage in clinical isolates of Staphylococcus epidermidis. Iranian J Med Sci 36(3):213–216

    Google Scholar 

  • Eliopoulos GM, Thau vin C, Gerson B, Moellering RC (1985) In vitro activity and mechanism of action of A21978C1, a novel cyclic lipopeptide antibiotic. Antimicrob Agents Chemother 27(3):357–362

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Endimiani A, Choudhary Y, Bonomo RA (2009) In vitro activity of NXL104 in combination with β-lactams against Klebsiella pneumoniae isolates producing KPC carbapenemases. Antimicrob Agents Chemother 53(8):3599–3601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • English AR, Retsema JA, Girard AE, Lynch JE, Barth WE (1978) CP-45,899, a beta-lactamase inhibitor that extends the antibacterial spectrum of beta-lactams: initial bacteriological characterization. Antimicrob Agents Chemother 14(3):414–419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fair RJ, Tor Y (2014) Antibiotics and bacterial resistance in the 21st Century. Perspectives in Medicinal Chemistry 6:25–64

    Article  PubMed  PubMed Central  Google Scholar 

  • Farber B, Eliopoulos G, Ward J, Ruoff K, Syriopoulou V, Moellering R (1983) Multiply resistant viridans streptococci: Susceptibility to beta-lactam antibiotics and comparison of penicillin-binding protein patterns. Antimicrob Agents Chemother 24(5):702–705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fass R (1983) In vitro activity of ciprofloxacin (Bay o 9867). Antimicrob Agents Chemother 24(4):568–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fass R (1991) In vitro activity of RP 59500, a semisynthetic injectable pristinamycin, against Staphylococci, Streptococci, and Enterococci. Antimicrob Agents Chemother 35(3):553–599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fass RJ, Prior RB (1989) Comparative in vitro activities of piperacillin-tazobactam and ticarcillin-clavulanate. Antimicrob Agents Chemother 33(8):1268–1274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fernández-Cuenca F, Martínez-Martínez L, Conejo MC, Ayala JA, Perea EJ, Pascual A (2003) Relationship between beta-lactamase production, outer membrane protein and penicillin-binding protein profiles on the activity of carbapenems against clinical isolates of Acinetobacter baumannii. J Antimicrob Chemother 51(3):565–574

    Article  CAS  PubMed  Google Scholar 

  • Ford CW, Hamel JC, Wilson DM, Moerman JK, Stapert D, Yancey Jr RJ, Hutchinson DK, Barbachyn MR, Brickner SJ (1996) In vivo activities of U-100592 and U-100766, novel oxazolidinone antimicrobial agents, against experimental bacterial infections. Antimicrob Agents Chemother 40(6):1508–1513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu KP, Neu HC (1978a) Azlocillin and mezlocillin: new ureido penicillins. Antimicrob Agents Chemother 13(6):930–938

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fu K, Neu H (1978b) Piperacillin, a new penicillin active against many bacteria resistant to other penicillins. Antimicrob Agents Chemother 13(3):358–367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fuchs PC, Barry AL, Thornsberry C, Jones RN (1984) In vitro activity of ticarcillin plus clavulanic acid against 632 clinical isolates. Antimicrob Agents Chemother 25(3):392–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ghose AK, Crippen GM (1987) Atomic physicochemical parameters for three-dimensional-structure-directed quatitative structure-activity relationships. 2. Modeling dispersive and hydrophobic interactions. J Chem Informat Model 27(1):21–35

    Article  CAS  Google Scholar 

  • Gilbert DN, Chambers HF, Eliopoulos GM, Saag MS, Pavia AT, Black D, Freedman DO, Kim K, Schwartz BS (2016) Guía Sanford: Guía de Terapéutica Antimicrobiana 2016, 46a ED. A.W.W.E. Editorial Médica, USA

    Google Scholar 

  • Gill VJ, Manning CB, Ingalls CM (1981) Correlation of penicillin minimum inhibitory concentrations and penicillin zone edge appearance with staphylococcal beta-lactamase production. J Clin Microbiol 14(4):437–440

    CAS  PubMed  PubMed Central  Google Scholar 

  • Goldstein EJ, Citron DM (1986) Comparative in vitro activities of amoxicillin-clavulanic acid and imipenem against anaerobic bacteria isolated from community hospitals. Antimicrob Agents Chemother 29(1):158–160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Haller I (1984) Importance of extracellular and cell-bound beta-lactamase in mediating resistance of Staphylococcus aureus to mezlocillin. Antimicrob Agents Chemother 25(1):125–127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hansch C, Fujita T (1964) J Am Chem Soc 86(8):1616–1626

    Article  CAS  Google Scholar 

  • Hebeisen P, Heinze-Krauss I, Angehrn P, Hohl P, Page MG, Then RL (2001) In vitro and in vivo properties of Ro 63-9141, a novel broad-spectrum cephalosporin with activity against methicillin-resistant staphylococci. Antimicrob Agents Chemother 45(3):825–836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henry D, Skidmore AG, Ngui-Yen J, Smith A, Smith JA (1985) In vitro activities of enoxacin, ticarcillin plus clavulanic acid, aztreonam, piperacillin, and imipenem and comparison with commonly used antimicrobial agents. Antimicrob Agents Chemother 28(2):259–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Héritier C, Poirel L, Fournier P-E, Claverie J-M, Raoult D, Nordmann P (2005) Characterization of the naturally occurring oxacillinase of Acinetobacter baumannii. Antimicrob Agents Chemother 49(10):4174–4179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Higgins PG, Wisplinghoff H, Stefanik D, Seifert H (2004) In vitro activities of the β-lactamase inhibitors clavulanic acid, sulbactam, and tazobactam alone or in combination with β-lactams against epidemiologically characterized multidrug-resistant Acinetobacter baumannii strains. Antimicrob Agents Chemother 48(5):1586–1592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoban DJ, Doern GV, Fluit AC, Roussel-Delvallez M, Jones RN (2001) Worldwide prevalence of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial Surveillance Program, 1997–1999. Clin Infect Dis 15(32):S81–S93

    Article  Google Scholar 

  • Ikeda F (1990) Intrinsic penicillin resistance in penicillinase-producing Neisseria gonorrhoeae strains. Microbiol Immunol 34(1):1–9

    Article  CAS  PubMed  Google Scholar 

  • Jacobs MR, Bajaksouzian S, Zilles A, Lin G, Pankuch GA, Appelbaum PC (1999) Susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae to 10 oral antimicrobial agents based on pharmacodynamic parameters: 1997 u.s. surveillance study. Antimicrob Agents Chemother 43(8):1901–1908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jacobs MR, Good CE, Windau AR, Bajaksouzian S, Biek D, Critchley IA, Sader HS, Jones RN (2010) Activity of ceftaroline against recent emerging serotypes of Streptococcus pneumoniae in the United States. Antimicrob Agents Chemother 54(6):2716–2719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones RN, Barry AL, Thornsberry C (1983) In vitro evaluation of three new macrolide antimicrobial agents, RU28965, RU29065, and RU29702, and comparisons with other orally administered drugs. Antimicrob Agents Chemother 24(2):209–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones RN, Fuchs PC, Sommers HM, Gavan TL, Al Barry, Gerlach EH (1980) Moxalactam (LY127935), a new semisynthetic 1-oxa-beta-lactam antibiotic with remarkable antimicrobial activity: in vitro comparison with cefamandole and tobramycin. Antimicrob Agents Chemother 17(4):750–756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones RN, Thornsberry C, Barry AL, Fuchs PC, Gavan TL, Gerlach EH (1977) Piperacillin (T-1220), a new semisynthetic penicillin: in vitro antimicrobial activity comparison with carbenicillin, ticarcillin, ampicillin, cephalothin, cefamandole and cefoxitin. J Antibiot 30(12):1107–1114

    Article  CAS  PubMed  Google Scholar 

  • Jorgensen JH, Doern GV, Maher LA, Howell AW, Redding JS (1990) Antimicrobial resistance among respiratory isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae in the United States. Antimicrob Agents Chemother 34(11):2075–2080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kasper DL, Hauser SL, Jameson JL, Fauci AS, Longo DL, Loscalzo J (2015) Harrison: Principios de medicina interna. McGraw-Hill, China, p 930–1102

    Google Scholar 

  • Kesado T, Hashizume T, Asahi Y (1980) Antibacterial activities of a new stabilized thienamycin, N-formimidoyl thienamycin, in comparison with other antibiotics. Antimicrob Agents Chemother 17(6):912–917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klevens RM, Morrison MA, Nadle J, Petit S, Gershman K, Ray S, Harrison LH, Lynfield R, Dumyati G, Townes JM, Craig AS, Zell ER, Fosheim GE, McDougal LK, Carey RB, Fridkin SK (2007) Invasive methicillin-resistant Staphylococcus aureus infections in the United States. JAMA 298(15):1763–1771

    Article  CAS  PubMed  Google Scholar 

  • Knox R, Smith JT (1963) Stability of methicillin and cloxacillin to staphylococcal penicillinase. Br Med J 27(2):205–207

    Article  Google Scholar 

  • Lacy MK, Lu W, Xu X, Tessier PR, Nicolau DP, Quintiliani R, Nightingale CH (1999) Pharmacodynamic comparisons of levofloxacin, ciprofloxacin, and ampicillin against Streptococcus pneumoniae in an in vitro model of infection. Antimicrob Agents Chemother 43(3):672–677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Larsson S, Walder MH, Cronberg SN, Forsgren AB, Moestrup T (1985) Antimicrobial susceptibilities of Listeria monocytogenes strains isolated from 1958 to 1982 in Sweden. Antimicrob Agents Chemother 28(1):12–14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leo A, Hansch C, Elkins D (1971) Partition coefficients and their uses. Chem Rev 71(6):525–616

    Article  CAS  Google Scholar 

  • Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46:3–26

    Article  CAS  PubMed  Google Scholar 

  • Marques de Cantú MJ (1998) Probabilidad y estadística para ciencias químico-biológicas. McGraw-Hill, Mexico, p 425–456, 471–486

    Google Scholar 

  • McCracken GH, Nelson JD, Thomas ML (1973) Discrepancy between carbenicillin and ampicillin activities against Enterococci and Listeria. Antimicrob Agents Chemother 3(3):343–349

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McWhinney PH, Patel S, Whiley RA, Hardie JM, Gillespie SH, Kibbler CC (1993) Activities of potential therapeutic and prophylactic antibiotics against blood culture isolates of viridans group streptococci from neutropenic patients receiving ciprofloxacin. Antimicrob Agents Chemother 37(11):2493–2495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miraglia GJ, Basch HI (1967) Activity of selected penicillins in vitro and in experimental bacterial infections in mice. Appl Microbiol 15(3):566–568

    CAS  PubMed  PubMed Central  Google Scholar 

  • Miyazaki M, Nagata N, Miyazaki H, Matsu K, Takata T, Tanihara S, Kamimura H (2014) Linezolid minimum inhibitory concentration (MIC) creep in methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates at a single Japanese center. Biol Pharm Bull 37(4):679–682

    Article  CAS  PubMed  Google Scholar 

  • Monif G, Clarck P, Shuster J, Baer H (1978) Susceptibility of the anaerobic bacteria, Group D Streptococci, Enterobacteriaceae, and Pseudomonas to semisynthetic penicillins: carbenicillin, piperacillin, and ticarcillin. Antimicrob Agents Chemother 14(5):643–649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moody JA, Peterson LR, Gerding DN (1985) In vitro activity of ciprofloxacin combined with azlocillin. Antimicrob Agents Chemother 28(6):849–850

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nelson C, Mason E, Kaplan SL (1994) Activity of oral antibiotics in middle ear and sinus infections caused by penicillin-resistant Streptococcus pneumoniae: implications for treatment. Pediatr Infect Dis J 13(7):585–589

    Article  CAS  PubMed  Google Scholar 

  • Neu HC (1982) Penicillins-new insights into their mechanisms of activity and clinical use. Bull New York Acad Med 58(8):681–695

    CAS  Google Scholar 

  • Neu HC, Aswapokee N, Fu KP, Aswapokee P (1979) Antibacterial activity of a new 1-oxa cephalosporin compared with that of other β-lactam compounds. Antimicrob Agents Chemother 16(2):141–149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neu HC, Fu KP, Aswapokee N, Aswapokee P, Kung K (1979) Comparative activity and β-lactamase stability of cefoperazone, a piperazine cephalosporin. Antimicrob Agents Chemother 16(2):150–157

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neu HC, Labthavikul P (1982) Comparative in vitro activity of N-formimidoyl thienamycin against Gram-positive and Gram-negative aerobic and anaerobic species and its beta-lactamase stability. Antimicrob Agents Chemother 21(1):180–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neu HC, Meropol NJ, Fu KP (1981) Antibacterial activity of ceftriaxone (Ro 13-9904), a beta-lactamase-stable cephalosporin. Antimicrob Agents Chemother 19(3):414–423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neu H, Winshell E (1972) Relation of 1-lactamase activity and cellular location to resistance of Enterobacter to penicillins and cephalosporins. Antimicrob Agents Chemotherapy 1(2):107–111

    Article  CAS  Google Scholar 

  • Nicolson K, Evans G, O´Toole P (1999) Potentiation of methicillin activity against methicillin-resistant Staphylococcus aureus by diterpenes. FEMS Microbiol Letters 179:233–239

    Article  CAS  Google Scholar 

  • Olsson B, Nord C-E, Wadström T (1976) Formation of Beta-Lactamase in Bacteroides fragilis: Cell-Bound and extracellular activity. Antimicrob Agents Chemother 9(5):727–735

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Osano E, Arakawa Y, Wacharotayankun R, Ohta M, Horii T, Ito H, Yoshimura F, Kato N (1994) Molecular characterization of an enterobacterial metallo beta-lactamase found in a clinical isolate of Serratia marcescens that shows imipenem resistance. Antimicrob Agents Chemother 38(1):71–78

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Overturf GD, Steinberg EA, Underman AE, Wilkins J, Leedom JM, Mathies Jr AW, Wehrle PF (1977) Comparative trial of carbenicillin and ampicillin therapy for purulent meningitis. Antimicrob Agents Chemother 11(3):420–426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Padrón JA, Pellón RF (2002) Molecular descriptor based on a molar refractivity partition using Randic-type graph-theoretical invariant. J Pharm Pharmaceut Sci 5(3):258–265

    Google Scholar 

  • París MM, Ramilo O, McCracken GH (1995) Management of meningitis caused by penicillin-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother 39(10):2171–2175

    Article  PubMed  PubMed Central  Google Scholar 

  • PC Spartan pro molecular modeling for the desktop (1999) Chemical & Engineering News Archive 77(17):2

    Article  Google Scholar 

  • Philippon LN, Naas T, Bouthors AT, Barakett V, Nordmann P (1997) OXA-18, a class D clavulanic acid-inhibited extended-spectrum beta-lactamase from Pseudomonas aeruginosa. Antimicrob Agents Chemother 41(10):2188–2195

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Poirel L, Le Thomas I, Naas T, Karim A, Nordmann P (2000) Biochemical sequence analyses of ges-1, a novel class an extended-spectrum β-lactamase, and the class 1 integron in52 from Klebsiella pneumoniae. Antimicrob Agents Chemother 44(3):622–632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quinn J, Miyashiro D, Sahm D, Flamm R, Bush K (1989) Novel plasmid-mediated beta-lactamase (TEM-10) conferring selective resistance to ceftazidime and aztreonam in clinical isolates of Klebsiella pneumoniae. Antimicrob Agents Chemother 33(9):1451–1456

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reading C, Cole M (1977) Clavulanic acid: a beta-lactamase-inhibiting beta-lactam from Streptomyces clavuligerus. Antimicrob Agents Chemother 11(5):852–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reimer LG, Mirrett S, Reller LB (1980) Comparison of in vitro activity of moxalactam (LY127935) with cefazolin, amikacin, tobramycin, carbenicillin, piperacillin, and ticarcillin against 420 blood culture isolates. Antimicrob Agents Chemother 17(3):412–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reimer LG, Stratton CW, Reller LB (1981) Minimum inhibitory and bactericidal concentrations of 44 antimicrobial agents against three standard control strains in broth with and without human serum. Antimicrob Agents Chemother 19(6):1050–1055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rolston KV, LeFrock JL, Schell RF (1982) Activity of nine antimicrobial agents against Lancefield group C and group G streptococci. Antimicrob Agents Chemother 22(5):930–932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sabath L, Garner C, Wilcox C, Finland M (1976) Susceptibility of Staphylococcus aureus and Staphylococcus epidermidis to 65 Antibiotics. Antimicrob Agents Chemother 9(6):962–969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sahm D, Jones M, Hickey M, Diakun D, Mani S, Thornsberry C (2000) Resistance surveillance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in Asia and Europe, 1997–1998. J Antimicrob Chemother 45(4):457–466

    Article  CAS  PubMed  Google Scholar 

  • Sanders CC (1981) Comparative activity of mezlocillin, penicillin, ampicillin, carbenicillin, and ticarcillin against Gram-positive bacteria and Haemophilus influenzae. Antimicrob Agents Chemother 20(6):843–846

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sawai T, Yoshida T (1982) A simple method for testing the efficacy of a β-lactamase inhibitor against β-lactamase-producing Gram-negative bacteria. J Antibiot 35(8):1072–1077

    Article  CAS  PubMed  Google Scholar 

  • Servicios de salud (2018) Datos estadísticos sobre principales problemas de salud pública. http://wwwssm.gob.mx/portal/index.php/2-uncategorised/11-salud-publica. Accessed 20 Jan 2019

  • Smith ECJ, Kaatz GW, Seo SM, Wareham N, Williamson EM, Gibbons S (2007) The phenolic diterpene totarol inhibits multidrug efflux pump activity in Staphylococcus aureus. Antimicrob Agents Chemother 51(12):4480–4483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith MB, March J (1992) March’s advanced organic chemistry: reactions, mechanisms, and structure. Chapters 1 and 9 John Wiley & Sons, Inc, USA, p 916–18. 363–374

    Google Scholar 

  • Suh B, Bae K, Kim J, Jeong S, Young D, Lee K (2010) Outbreak of meropenem-resistant Serratia marcescens comediated by chromosomal AmpC beta-lactamase overproduction and outer membrane protein loss. Antimicrob Agents Chemother 54(12):5057–5061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sutherland R, Croydon EAP, Rolinson GN (1970) Flucloxacillin, a new isoxazolyl penicillin, compared with oxacillin, cloxacillin, and dicloxacillin. Br Med J 4(5733):455–460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sutherland R, Croydon EAP, Rolinson GN (1972) Amoxycillin: A new semi-synthetic penicillin. Br Med J 3(5817):13–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takata N, Suginaka H, Kotani S, Ogawa M, Kosaki G (1981) Beta-Lactam resistance in Serratia marcescens: comparison of action of benzylpenicillin, apalcillin, cefazolin, and ceftizoxime. Antimicrob Agents Chemother 19(3):397–401

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka H, Sato M, Fujiwara S, Hirata M, Etoh H, Takeuchi H (2002) Antibacterial activity of isoflavonoids isolated from Erythrina variegata against methicillin-resistant Staphylococcus aureus. Lett Appl Microbiol 35:494–498

    Article  CAS  PubMed  Google Scholar 

  • Taylor PC, Schoenknecht FD, Sherris JC, Linner EC (1983) Determination of minimum bactericidal concentrations of oxacillin for Staphylococcus aureus: influence and significance of technical factors. Antimicrob Agents Chemother 23(1):142–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teng LJ, Hsueh PR, Chen YC, Ho SW, Luh KT (1998) Antimicrobial susceptibility of viridans group streptococci in Taiwan with an emphasis on the high rates of resistance to penicillin and macrolides in Streptococcus oralis. J Antimicrob Chemother 41(6):621–627

    Article  CAS  PubMed  Google Scholar 

  • Thijssen HHW, Mattie H (1976) Active metabolites of isoxazolylpenicillins in humans. Antimicrob Agents Chemother 10(3):441–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomson KS, Moland ES (2004) CS-023 (R-115685), a novel carbapenem with enhanced in vitro activity against oxacillin-resistant staphylococci and Pseudomonas aeruginosa. J Antimicrob Chemother 54(2):557–562

    Article  CAS  PubMed  Google Scholar 

  • Toma E, Barriault D (1995) Antimicrobial activity of fusidic acid and disk diffusion susceptibility testing criteria for Gram-positive cocci. J Clin Microbiol 33(7):1712–1715

    CAS  PubMed  PubMed Central  Google Scholar 

  • Toshinobu H, Arakawa Y, Ohta M, Ichiyama S, Wacharotayankun R, Kato N (1993) Plasmid-mediated AmpC-type 1-lactamase isolated from Klebsiella pneumoniae confers resistance to broad-spectrum β-lactams, including moxalactam. Antimicrob Agents Chemother 37(5):984–90

    Article  Google Scholar 

  • Ubukata K, Nonoguchi R, Matsuhashi M, Konno M (1989) Expression and inducibility in Staphylococcus aureus of the mecA gene, which encodes a methicillin-resistant s. aureus-specific penicillin-binding protein. J Bacteriol 171(5):2882–2885

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verbist L (1978) In vitro activity of piperacillin, a new semisynthetic penicillin with an unusually broad spectrum of activity. Antimicrob Agents Chemother 13(3):549–357

    Article  Google Scholar 

  • Vouillamoz J, Moreillon P, Giddey M, Entenza JM (2006) Efficacy of daptomycin in the treatment of experimental endocarditis due to susceptible and multidrug-resistant enterococci. J Antimicrob Chemother 58(6):1208–1214

    Article  CAS  PubMed  Google Scholar 

  • Watanakunakorn C, Glotzbecker C (1979) Comparative in vitro activity of LY 127935 (6059-s), seven cephalosporins, three aminoglycosides, carbenicillin, and ticarcillin. J Antibiot 32(10):1019–1024

    Article  CAS  PubMed  Google Scholar 

  • White GW, Malow JB, Zimelis VM, Pahlavanzadeh H, Panwalker AP, Jackson GG (1979) Comparative in vitro activity of azlocillin, ampicillin, mezlocillin, piperacillin, and ticarcillin, alone and in combination with an aminoglycoside. Antimicrob Agents Chemother 15(4):540–543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williamson R, Hakenbeck R, Tomasz A (1980) In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae. Antimicrob Agents Chemother 18(4):629–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • World Health Organization (2018a) Wide differences in antibiotic use between countries, according to new data from WHO. https://www.who.int/medicines/areas/rational_use/oms-amr-amc-report-2016-2018-media-note/en/. Accessed 8 Jun 2019

  • World Health Organization (2018b) The top 10 causes of death. https://www.who.int/en/news-room/fact-sheets/detail/the-top-10-causes-of-death. Accessed 30 Jan 2019

  • World Health Organization (2015) WHO publishes a set of best practices for the naming of new human infectious diseases. https://www.who.int/es/news-room/detail/08-05-2015-who-issues-best-practices-for-naming-new-human-infectious-diseases. Accessed Mar 2019

  • Yang YJ, Wu PJ, Livermore DM (1990) Biochemical characterization of a beta-lactamase that hydrolyzes penems and carbapenems from two Serratia marcescens isolates. Antimicrob Agents Chemother 34(5):755–758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yotsuji A, Minami S, Inoue M, Mitsuhashi S (1983) Properties of novel β-lactamase produced by Bacteroides fragilis. Antimicrob Agents Chemother 24(6):925–929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu W, Ji J, Xiao T, Ying C, Fang J, Shen P, Xiao Y (2017) Determining optimal dosing regimen of oral administration of dicloxacillin using Monte Carlo simulation. Drug Des, Devel Ther 2017(11):1951–1956

    Article  Google Scholar 

  • Zurenko GE, Yagi BH, Schaadt RD, Allison JW, Kilburn JO, Glickman SE, Hutchinson DK, Barbachyn MR, Brickner SJ (1996) In vitro activities of U-100592 and U-100766, novel oxazolidinone antibacterial agents. Antimicrob Agents Chemother 40(4):839–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by Consejo Nacional de Ciencia y Tecnología (CONACyT; No. 257364) and SIP Project of Instituto Politécnico Nacional (No. 20181505).

Author information

Authors and Affiliations

  1. Departamento de Farmacología. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, S/N, México, D.F., 11340, Mexico

    J. R. Morán-Díaz & J. A. Guevara-Salazar

  2. Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación Manuel Carpio y Plan de Ayala, México, D.F., 11340, Mexico

    H. A. Jiménez-Vázquez

  3. Sección de Ciencias Biológicas y de la Salud Humana, Departamento de Ciencias Químico-Biológicas, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Av. 1 de Mayo s/n, Santa María las Torres, Cuautitlán Izcalli, 54740, Mexico

    R. Gómez-Pliego

  4. Laboratorio de Enfermedades Crónico-Degenerativas y Sección de Estudios de Posgrado e Investigación. Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, México, D.F., 11340, Mexico

    M. G. Arellano-Mendoza

  5. Laboratorio de Química Orgánica, Centro de Investigación en Ciencia Aplicada y Tecnología Avanzada, Unidad Legaria, Instituto Politécnico Nacional, Legaria No. 694, México, D.F., 11500, Mexico

    D. Quintana-Zavala

Authors
  1. J. R. Morán-Díaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. A. Jiménez-Vázquez
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Gómez-Pliego
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. G. Arellano-Mendoza
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. D. Quintana-Zavala
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. A. Guevara-Salazar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to D. Quintana-Zavala or J. A. Guevara-Salazar.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Morán-Díaz, J.R., Jiménez-Vázquez, H.A., Gómez-Pliego, R. et al. Correlation study of antibacterial activity and spectrum of Penicillins through a structure-activity relationship analysis. Med Chem Res 28, 1529–1546 (2019). https://doi.org/10.1007/s00044-019-02391-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-019-02391-9

Keywords

Search

Navigation