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In vitro antimicrobial activity of o-phenylenediamine-tert-butyl-N-1,2,3-triazole carbamate analogs

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Abstract

In an attempt to design and synthesize effective antimicrobial agents using click chemistry, mono- and di-alkyne-substituted monoboc protected o-phenylenediamines were reacted with different substituted aryl azides which yielded 18 new compounds (4a–4k and 5a–5f, 5l). Structures of all newly synthesized compounds were established by 1H and 13C NMR analysis. The intermediate compound 1 was also confirmed by X-ray crystallography. The title compounds were screened for their antibacterial activity against Gram +ve bacteria (Staphylococcus aureus and Enterococcus faecalis), Gram −ve bacteria (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), and their antifungal profile were tested on (Candida tropicalis, Candida albicans, Candida krusei, and Cryptococcus neoformans) as well as on molds such as (Aspergillus niger, Aspergillus fumigatus). The compounds 4k and 5f both showed maximum potency against S. aureus (ATCC 25323) strain with MIC value of 6.25 µg/ml, which is comparable with standard drug ciprofloxacin (MIC 6.25 µg/ml) while remaining compounds showed moderate to weak activity. Further, all compounds showed average antifungal activity in the range of 100–200 µg/ml.

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References

  • Agarwal A, Singh MK, Awasthi SK (2011a) 1-Prop-2-ynyl-1H-benzimidazol-2-amine. Acta Cryst E67:o3213–o3214

    Google Scholar 

  • Agarwal A, Singh MK, Singh S, Bhattacharya S, Awasthi SK (2011b) N-(Prop-2-yn-1-yl)-1,3-benzothiazol-2-amine. Acta Cryst E67:o2637–o2638

    Google Scholar 

  • Andre A, Gerard N (1969) 1-(Carboxyalkyl)-2-methyl-3-[substituted benzoyl (and thiobenzoyl)]indoles Ger. Offen (Roussel–UCLAF) DE 1901167 A 19691211

  • Bag SS, Matsumoto K, Talukdar S, Kundu R (2013) Triazolyl donor/acceptor chromophore decorated unnatural nucleosides and oligonucleotides with duplex stability comparable to that of a natural adenine/thymine pair. J Org Chem 78:278–291

    Article  CAS  PubMed  Google Scholar 

  • Banu KM, Dinakar A, Ananthanarayanan C (1999) Synthesis, characterization, antimicrobial studies and pharmacological screening of some substituted 1,2,3-triazoles. Indian J Pharm Sci 61:202–205

    CAS  Google Scholar 

  • Biagi G, Calderone V, Giorgi I, Livi O, Martinotti E, Martelli A, Nardi A (2004) 1,5-Diarylsubstituted 1,2,3-triazoles as potassium channel activators. VI. Farmaco 59:397–404

    Article  CAS  PubMed  Google Scholar 

  • Bickoff EM, Livingston AL, Guggolz J, Thompson CR (1952) Comparative evaluation of antioxidants for carotene. J Am Oil Chem Soc 29:445–446

    Article  CAS  Google Scholar 

  • Bouabdallah I, Barek LAM, Zyad A, Ramdani A, Zidane I, Melhaoui A (2006) Anticancer effect of three pyrazole derivatives. Nat Prod Res 20:1024–1030

    Article  CAS  PubMed  Google Scholar 

  • Chan DPY, Shoichet MS, Owen SC (2013) Double click: dual functionalized polymeric micelles with antibodies and peptides. Bioconjug Chem 24:105–113

    Article  CAS  PubMed  Google Scholar 

  • Chen M, Lu S, Yuan G, Yang S, Du X (2000) Synthesis and antibacterial activity of some heterocyclic β-enamino ester derivatives with 1,2,3-triazole. Heterocycl Commun 6:421–426

    CAS  Google Scholar 

  • Danoun S, Baziard-Mouysset G, Stigliani JL, Payard M, Selkti M, Viossat B, Tomas A (1998) Addition of diazomethane to 3 and 4-nitrophthalodinitriles. Heterocycl Commun 4:45–51

    CAS  Google Scholar 

  • Diana GD, Nitz TJ (1993) Preparation of [(1,2,4-oxadiazolylphenoxy)alkyl]isoxazoles and their use as antiviral agents. Eur Pat Appl EP 566199(A1):19931020

    Google Scholar 

  • Dixit SK, Mishra N, Sharma M, Singh S, Agarwal A, Awasthi SK, Bhasin VK (2012) Synthesis and in vitro antiplasmodial activities of fluoroquinolone analogs. Eur J Med Chem 51:52–59

    Article  CAS  PubMed  Google Scholar 

  • Eicher T, Hauptmann S (2003) The Chemistry of Heterocycles:Structure, Reactions, Syntheses and Applications, 2nd edn. Wiley-VCH, Weinheim

    Book  Google Scholar 

  • Friedemann MN, Robinson SW, Gerhardt G (1996) o-Phenylenediamine-modified carbon fiber electrodes for the detection of nitric oxide. Anal Chem 68:2621–2628

    Article  CAS  PubMed  Google Scholar 

  • Huang Y-B, Tang G-R, Jin G-Y, Jin G-X (2007) Binuclear nickel and copper complexes with bridging 2,5-diamino-1,4-benzoquinonediimines: synthesis, structures, and catalytic olefin polymerization. Organometallics 27:259–269

    Article  Google Scholar 

  • Hueber-Becker F, Nohynek GJ, Meuling WJ, Benech-Kieffer F, Toutain H (2004) Human systemic exposure to a [14C]-para-phenylenediamine-containing oxidative hair dye and correlation with in vitro percutaneous absorption in human or pig skin. Food Chem Toxicol 42:1227–1236

    Article  CAS  PubMed  Google Scholar 

  • Kahl T, Schröder KW, Lawrence FR, Marshall WJ, Höke H, Jäckh R (2007) “Aniline” in Ullmann’s Encyclopedia of Industrial Chemistry. John Wiley and Sons, New York. doi:10.1002/14356007.a02_3032

    Google Scholar 

  • Kang IJ, Lee MH (2006) Quantification of para-phenylenediamine and heavy metals in henna dye. Contact Dermat 55:26–29

    Article  CAS  Google Scholar 

  • Kolb HC, Sharpless KB (2003) The growing impact of click chemistry on drug discovery. Drug Discov Today 8:1128–1137

    Article  CAS  PubMed  Google Scholar 

  • Kolb HC, Finn MG, Sharpless KB (2001) Click chemistry: diverse chemical function from a few good reactions. Angew Chem Int Ed 40:2004–2021

    Article  CAS  Google Scholar 

  • Krüger RH, Boissiére C, Klein-Hartwig K, Kretzschmar HJ (2005) New phenylenediamine antiozonants for commodities based on natural and synthetic rubber. Food Addit Contam 22:968–974

    Article  PubMed  Google Scholar 

  • Lilienkampf A, Mao J, Wan B, Wang Y, Franzblau SG, Kozikowski AP (2009) Structure–activity relationships for a series of quinoline-based compounds active against replicating and nonreplicating Mycobacterium tuberculosis. J Med Chem 52:2109–2118

    Article  CAS  PubMed  Google Scholar 

  • Mahawer C, Singh MK, Agarwal A (2013) Crystal structure of {4-[3-(4-Fluoro-phenyl)-acryloyl]-phenyl}-carbamic acid tert-butyl ester. Proc Natl Acad Sci India A. doi:10.1007/s40010-013-0077-5

    Google Scholar 

  • Manfredini S, Vicentini CB, Manfrini M, Bianchi N, Rutigliano C, Mischiati C, Gambari R (2000) Pyrazolo-triazoles as light activable DNA cleaving agents. Bioorg Med Chem 8:2343–2346

    Article  CAS  PubMed  Google Scholar 

  • Meier R (1986) Preparation of fluorinated phenylalkyltriazoles as anticonvulsants and pharmaceutical compositions containing them. Eur Pat Appl EP 199262(A2):19861029

    Google Scholar 

  • Nielsen SF, Larsen M, Boesen T, Schonning K, Kromann H (2005) Cationic chalcone antibiotics. Design, synthesis and mechanism of action. J Med Chem 48:2667–2677

    Article  CAS  PubMed  Google Scholar 

  • Niemann GJ, Dekker J (1966) Activity against rust and powdery mildew of some para-phenylenediamines and related compounds. Neth J Plant Pathol 72:213–221

    Article  CAS  Google Scholar 

  • Obaseiki-Ebor EE, Odukoya K, Telikepalli H, Mitscher LA, Shankel DM (1993) Antimutagenic activity of extracts of leaves of 4 common edible vegetable plants in Nigeria (West-Africa). Mutat Res 302:109–117

    Article  CAS  PubMed  Google Scholar 

  • Passannanti A, Diana P, Barraja P, Mingoia F, Lauria A, Cirrincione G (1998) Pyrrolo[2,3-d][1,2,3]triazoles as potential antineoplastic agents. Heterocycles 48:1229–1235

    Article  CAS  Google Scholar 

  • Patai S (1994) Chemistry of Triple-Bonded Functional Groups. Wiley, New York

    Book  Google Scholar 

  • Pauling L, Brockway LO (1934) A study of the methods of interpretation of electron-diffraction photographs of gas molecules, with results for benzene and carbon tetrachloride. J Chem Phys 2:867–881

    Article  CAS  Google Scholar 

  • Raut CN, Bagul SM, Janrao RA, Vaidya SD, Kumar VBS, Mahulikar PP (2010) Synthesis of some novel N-alkyl/acyl/aroyl 2-(chroman/6-bromochroman-2-yl)-1H-benzimidazoles using ionic liquids and their antibacterial activity. J Heterocycl Chem 47:582–588

    CAS  Google Scholar 

  • Robertson KN, Knop O, Cameron TS (2003) C–H···H–C interactions in organoammonium tetraphenylborates: another look at dihydrogen bonds. Can J Chem 81:727–743

    Article  CAS  Google Scholar 

  • Rostovtsev VV, Green LG, Fokin VV, Sharpless KB (2002) A stepwise Huisgen cycloaddition process: copper(I)-catalyzed regioselective “ligation” of azides and terminal alkynes. Angew Chem Int Ed 41:2596–2599

    Article  CAS  Google Scholar 

  • Sachin HP, Khan MHM, Bhujangaiah NS (2009) Surface modification of mild steel by orthophenylenediamine and its corrosion study. Int J Electrochem Sci 4:134–143

    CAS  Google Scholar 

  • Sanghvi YS, Bhattacharya BK, Kini GD, Matsumoto SS, Larson SB, Jolley WB, Robins RK, Revankar GR (1990) Growth inhibition and induction of cellular differentiation of human myeloid leukemia cells in culture by carbamoyl congeners of ribavirin. J Med Chem 33:336–344

    Article  CAS  PubMed  Google Scholar 

  • Sheldrick GM (2008) A short history of SHELX. Acta Cryst A64:112–122

    Article  Google Scholar 

  • Sheremet EA, Tomanov RI, Trukhin EV, Berestovitskaya VM (2004) Synthesis of 4-aryl-5-nitro-1,2,3-triazoles. Russ J Org Chem 40:594–595

    Article  CAS  Google Scholar 

  • Singh MK, Agarwal A, Awasthi SK (2011a) Benzyl N-(3-chloro-4-fluorophenyl)carbamate. Acta Cryst E 67:o1137

    Article  CAS  Google Scholar 

  • Singh MK, Agarwal A, Mahawara C, Awasthi SK (2011b) tert-Butyl N-{2-[bis(prop-2-yn-1-yl)amino]phenyl}carbamate. Acta Cryst E 67:o1382

    Article  CAS  Google Scholar 

  • Singh S, Singh MK, Agarwal A, Awasthi SK (2011c) 2-(4-Chlorophenyl)chromen-4-one. Acta Cryst E 67:o3163

    Article  CAS  Google Scholar 

  • Singh S, Singh MK, Agarwal A, Hussain F, Awasthi SK (2011d) (2E)-1-(4-Aminophenyl)-3-(2,4-dichlorophenyl)prop-2-en-1-one. Acta Cryst E67:o1616–o1617

    Google Scholar 

  • Singh MK, Tilak R, Nath G, Awasthi SK, Agarwal A (2013) Design, synthesis and antimicrobial activity of novel benzothiazole analogs. Eur J Med Chem 63:635–644

    Article  CAS  PubMed  Google Scholar 

  • Varma RS (1999) Solvent-free synthesis of heterocyclic compounds using microwaves. J Heterocycl Chem 36:1565–1571

    Article  CAS  Google Scholar 

  • Wiegand I, Hilpert K, Hancock REW (2008) Agar and broth dilution methods to determine the minimal inhibitory concentration (MIC) of antimicrobial substances. Nat Protoc 3:163–175

    Article  CAS  PubMed  Google Scholar 

  • Yasuo S, Akio A, Yashiro F, Koshida S, Wakao M, Nishimura T, Kusumoto S, Sobel M (2006) Immobilization and clustering of structurally defined oligosaccharides for sugar chips: an improved method for surface plasmon resonance analysis of protein–carbohydrate interactions. Bioconjug Chem 17:1125–1135

    Article  Google Scholar 

  • Zabula AV, Hahn FE (2008) Mono- and bidentate benzannulated N-heterocyclic germylenes, stannylenes and plumbylenes. Eur J Inorg Chem 33:5165–5179

    Article  Google Scholar 

  • Zeng XH, Liu M, Ding MW, He HW (2010) Facile synthesis of 2-alkylthio-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones. Synth Commun 40:1453–1460

    Article  CAS  Google Scholar 

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Acknowledgments

AA is thankful to (UGC), New Delhi, India (Scheme No. 34-3212008) and Banaras Hindu University Varanasi, UP, India, respectively, for financial support. MKS is thankful to Banaras Hindu University, Varanasi, India for financial support. This work was in partly supported by GN and RT by the Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, UP, India.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Institute of Medical Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India

    Manavendra Kumar Singh & Alka Agarwal

  2. Department of Microbiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India

    Mayank Gangwar, Dharmendra Kumar, Ragini Tilak & Gopal Nath

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  1. Manavendra Kumar Singh
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  2. Mayank Gangwar
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Correspondence to Alka Agarwal.

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Singh, M.K., Gangwar, M., Kumar, D. et al. In vitro antimicrobial activity of o-phenylenediamine-tert-butyl-N-1,2,3-triazole carbamate analogs. Med Chem Res 23, 4962–4976 (2014). https://doi.org/10.1007/s00044-014-1063-4

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