Skip to main content

Advertisement

SpringerLink
Log in

Synthesis and biological evaluation of novel hydroquinone dimethyl ethers as potential anticancer and antimicrobial agents

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

Abstract

The synthesis of two novel series of quinol dimethyl ethers linked to either various functionalities or to some biologically active nitrogenous heterocycles is described. Nine of the newly synthesized quinol dimethyl ethers 5a, b, 9b, 10a, d, 12a, b, and 13a, b were selected by the NCI and were tested initially at a single high dose (10 μM) in the full NCI 60 cell panel. Four of the screened quinol dimethyl ethers bearing unsubstituted phenylhydrazone 5a, 4-chlorophenylhydrazone 5b, 4-chlorophenyl-3-sulfanyl-1,2,4-triazole 9b, as well as 4-chloroanilino-1,3,4-oxadiazole 12b moieties satisfied the threshold antitumor screen. 4-Chlorophenylhydrazone 5b showed very promising results and accordingly was chosen for in vivo antitumor screening. Thus, compound 5b of the series could be considered as the potential lead for development of novel anticancer agents. In addition, compounds 5a–c, 6a–c, 9a–c, 10a, b, d, e, g, h, 11a–c, 12a–c, and 13a–c were screened for their in vitro antimicrobial activity. Some of the tested compounds exhibited special high activity comparable to the reference ampicillin against Pseudomonas aeruginosa and Escherichia coli.

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

Scheme 1
Scheme 2
Fig. 1

Similar content being viewed by others

References

  • Akbas E, Berber I (2005) Antibacterial and antifungal activities of new pyrazolo[3,4-d]pyridazin derivatives. Eur J Med Chem 40(4):401–405. doi:10.1016/j.ejmech.2004.12.001

    Article  PubMed  CAS  Google Scholar 

  • Amr AEE, Mohamed SF, Abdel-Hafez NA, Abdalla MM (2008) Antianxiety activity of pyridine derivatives synthesized from 2-chloro-6-hydrazino-isonicotinic acid hydrazide. Monatsh Chem 139(2):1491–1498. doi:10.1007/s00706-008-0949-6

    Article  CAS  Google Scholar 

  • Ashour HMA, Abdel Wahab AE (2009) Synthesis and biological evaluation of novel pyrazoles and pyrazolo[3,4-d]pyrimidines incorporating a benzenesulfonamide moiety. Arch Pharm Chem Life Sci 342(4):238–252. doi:10.1002/ardp.200800178

    Article  CAS  Google Scholar 

  • Barrero AF, Alvarez-Manzaneda EJ, Herrador MM, Chahboun R, Galera P (1999) Synthesis and antitumoral activities of marine ent-chromazonarol and related compounds. Bioorg Med Chem Lett 9(16):2325–2328. doi:10.1016/S0960-894X(99)00382-0

    Article  PubMed  CAS  Google Scholar 

  • Boyd MR, Paull KD (1995) Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev Res 34(2):91–109. doi:10.1002/ddr.430340203

    Article  CAS  Google Scholar 

  • Chaaban I, El-Khawass SM, Mahran M, El-Sayed OA, El-Saidi H, Aboul-Enen H (2006) Hydroquinones, benzoquinones and quinol dimethyl ethers substituted at the 2-position by a heterocyclic ring: synthesis and evaluation for potential antimicrobial activity. Alex J Pharm Sci 20(2):107–114

    CAS  Google Scholar 

  • Chaaban I, El-Khawass SM, Mahran M, El-Sayed OA, El-Saidi H, Aboul-Enen H (2007) Design, synthesis, and in vitro evaluation of cytotoxic activity of new substituted 1,4-benzoquinones and hydroquinones. Med Chem Res 16(2):49–77. doi:10.1007/s00044-007-9001-3

    Article  CAS  Google Scholar 

  • Chornous VA, Bratenko MK, Vovk MV, Sidorchuk II (2001) Synthesis and antimicrobial activity of pyrazole-4-carboxylic acid hydrazides and N-(4-pyrazoyl)hydrazones of aromatic and heteroaromatic aldehydes. Pharm Chem J 35(4):203–205. doi:10.1023/A:1010432029236

    Article  CAS  Google Scholar 

  • Cordero CP, Gómez-González S, León-Acosta CJ, Morantes-Medina SJ, Aristizabal FA (2004) Cytotoxic activity of five compounds isolated from colombian plants. Fitoterapia 75(2):225–227. doi:10.1016/j.fitote.2003.12.017

    Article  PubMed  CAS  Google Scholar 

  • Cozzi P (2003) The discovery of a new potential anticancer: a case history. Il Farmaco 58(3):213–220. doi:10.1016/S0014-827X(03)00014-4

    Article  PubMed  CAS  Google Scholar 

  • Duran A, Dogan HN, Rollas S (2002) Synthesis and preliminary anticancer activity of new 1,4-dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-5H-1,2,4-triazoline-5-thiones. Il Farmaco 57(7):559–564. doi:10.1016/S0014-827X(02)01248-X

    Article  PubMed  CAS  Google Scholar 

  • French GL (2006) Bactericidal agents in the treatment of MRSA infections—the potential role of daptomycin. J Antimicrob Chemother 58:1107–1117

    Article  PubMed  CAS  Google Scholar 

  • Grever MR, Schepartz SA, Chabner BA (1992) The National Cancer Institute: cancer drug discovery and development program. Semin Oncol 19(6):622–638

    PubMed  CAS  Google Scholar 

  • Gribkov AA, Borovkov VV, Evstigneeva RP, Sakata Y (1994) Synthesis of rigidly linked triad molecules based on octaalkylporphyrin, capable of multistep electron transfer. Chem Heterocycl Compd 30(8):905–915. doi:10.1007/BF01165028

    Article  Google Scholar 

  • Harada R, Kondo H (1968) Synthesis of α, β-unsaturated carboxylic hydrazides. Bull Chem Soc Jpn 41:2521–2523

    Article  CAS  Google Scholar 

  • Havaldar FH, Patil AR (2008) Syntheses of 1,2,4-triazole derivatives and their biological activity. J Chem 5(2):347–354

    CAS  Google Scholar 

  • Huang CP, Fang W-H, Lin L-I, Chiou RY, Kan L-S, Chi N-H, Chen Y-R, Lin T-Y, Lin S-B (2008) Anticancer activity of botanical alkyl hydroquinones attributed to topoisomerase II poisoning. Toxicol Appl Pharmacol 227(3):331–338

    Article  PubMed  CAS  Google Scholar 

  • Ichiro H, Masao Y, Yuichi S, Hitoshi K, Tatsuo T, Hiroshi K, Takafumi K, Yoshikazu U 2006 Sankyo Company Ltd., Japan JP 2004-236626 (PCT/JP05/014633), C. A., 144:233080

  • Jain SR, Kar A (1971) The antibacterial activity of some essential oils and their combinations. Planta Med 20(2):118–123

    Article  PubMed  CAS  Google Scholar 

  • Jin L, Chen J, Song B, Chen Z, Yang S, Li Q, Hu D, Xu R (2006) Synthesis, structure, and bioactivity of N′-substituted benzylidene-3,4,5-trimethoxybenzohydrazide and 3-acetyl-2-substituted phenyl-5-(3,4,5-trimethoxyphenyl)-2,3-dihydro-1,3,4-oxadiazole derivatives. Bioorg Med Chem Lett 16(19):5036–5040. doi:10.1016/j.bmcl.2006.07.048

    Article  PubMed  CAS  Google Scholar 

  • Johnston SRD, Ford H, Ross P (2005) The Royal Marsden hospital hand book of cancer chemotherapy In: Brighton D, Wood M (eds) Elsevier Churchill Livingstone, London, New York, Oxford, p 1–17

  • Joshi SD, Vagdevi HM, Vaidya VP, Gadaginamath GS (2008) Synthesis of new 4-pyrrol-1-yl benzoic acid hydrazide analogs and some derived oxadiazole, triazole and pyrrole ring systems: a novel class of potential antibacterial and antitubercular agents. Eur J Med Chem 43(9):1989–1996. doi:10.1016/j.ejmech.2007.11.016

    Article  PubMed  CAS  Google Scholar 

  • Kadi AA, El-Brollosy NR, Al-Deeb OA, Habib EE, Ibrahim TM, El-Emam AA (2007) Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles. Eur J Med Chem 42(2):235–242. doi:10.1016/j.ejmech.2006.10.003

    Article  PubMed  CAS  Google Scholar 

  • Kilcigil GA, Kuş C, Altanlar N, Özbey S (2005) Synthesis and antimicrobial evaluation of some new 2-(2-(p-chlorophenyl)benzimidazol-1-ylmethyl)-5-substitutedamino-[1,3,4]-thiadiazoles. Turk J Chem 29:153–162

    Google Scholar 

  • Kumar SK, Hager E, Pettit C, Gurulingappa H, Davidson NE, Khan SR (2003) Design, synthesis, and evaluation of novel boronic-chalcone derivatives as antitumor agents. J Med Chem 46(14):2813–2815. doi:10.1021/jm030213

    Article  PubMed  CAS  Google Scholar 

  • Lee L, Robb M, Lee M, Davis R, Mackay H, Chavda S, Babu B, O’Brien EL, Risinger AL, Mooberry SL, Lee M (2010) Design, synthesis and biological evaluations of 2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoline analogs of combretastatin-A4J. Med Chem 53(1):325–334. doi:10.1021/jm901268n

    Article  CAS  Google Scholar 

  • Liu X, Ou Y, Chen S, Lu X, Cheng H, Jia X, Wang D, Zhou GC (2010) Synthesis and inhibitory evaluation of cyclohexen-2-yl- and cyclohexyl-substituted phenols and quinones to endothelial cell and cancer cells. Eur J Med Chem 45(6):2147–2153

    Article  PubMed  CAS  Google Scholar 

  • Matysiak J, Opolski A (2006) Synthesis and antiproliferative activity of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. Bioorg Med Chem 14(13):4483–4489. doi:10.1016/j.bmc.2006.02.027

    Article  PubMed  CAS  Google Scholar 

  • Metwally KA, Abdel-Aziz LM, Lashine ESM, Husseiny MI, Badawy RH (2006) Hydrazones of 2-aryl-quinoline-4-carboxylic acid hydrazides: synthesis and preliminary evaluation as antimicrobial agents. Bioorg Med Chem 14(24):8675–8682. doi:10.1016/j.bmc.2006.08.022

    Article  PubMed  CAS  Google Scholar 

  • Monks A, Scudiero D, Skehan P, Shoemaker R, Paull K, Vistica D, Hose C, Langley J, Cronise P, Vaigro-Wolff A, Gray-Goodrich M, Campbell H, Mayo J, Boyd M (1991) Feasibility of a high-flux anticancer drug screen using a diverse panel of cultured human tumor cell lines. J Natl Cancer Inst 38(11):757–766. doi:10.1093/jnci/83.11.757

    Article  Google Scholar 

  • Ong CW, Hwang JD, Chern JW (1988) Synthesis and biological evaluation of (E, E)-3,6-bis(2,5-dimethoxybenzylidene-2,5-dioxopiperazine). J Med Sci 9:175–180

    Google Scholar 

  • Pingaew R, Prachayasittikul S, Ruchirawat S (2010) Synthesis, cytotoxic and antimalarial activities of benzoyl thiosemicarbazone analogs of isoquinoline and related compounds. Molecules 15(2):988–996. doi:10.3390/molecules15020988

    Article  PubMed  CAS  Google Scholar 

  • Pintilie O, Profire L, Sunel V, Popa M, Pui A (2007) Synthesis and antimicrobial activity of some new 1,3,4-thiadiazole and 1,2,4-triazole compounds having a d, l-methionine moiety. Molecules 12(1):103–113. doi:10.3390/12010103

    Article  PubMed  CAS  Google Scholar 

  • Rollas S, Gulerman N, Erdeniz H (2002) Synthesis and antimicrobial activity of some new hydrazones of 4-fluorobenzoic acid hydrazide and 3-acetyl-2,5-disubstituted-1,3,4-oxadiazolines. Il Farmaco 57(2):171–174. doi:10.1016/S0014-827X(01)01192-2

    Article  PubMed  CAS  Google Scholar 

  • Rostom SAF, Ashour HMA, Abd El Razik HA (2009) Synthesis and biological evaluation of some novel polysubstituted pyrimidine derivatives as potential antimicrobial and anticancer agents. Arch Pharm Chem Life Sci 342(5):299–310. doi:10.1002/ardp.200800223

    Article  CAS  Google Scholar 

  • Scott AC (1989) In: Collee JG, Duguid JP, Fraser AG, Marmion BP (eds) Mackie & McCartney practical medical microbiology, vol 2, 13th edn. Churchill Livingstone, New York, pp 161–181

    Google Scholar 

  • Tapia RA, Prieto Y, Pautet F, Walchshofer N, Fillion H, Fenet B, Sarciron ME (2003) Synthesis and antiprotozoal evaluation of benzothiazolopyrroloquinoxalinones, analogues of kuanoniamine A. Bioorg Med Chem 11:3407–3412. doi:10.1016/S0968-0896(03)00311-0

    Article  PubMed  CAS  Google Scholar 

  • Tu HY, Huang AM, Hour TC, Yang SC, Pu YS, Lin CN (2010) Synthesis and biological evaluation of 2′,5′-dimethoxychalcone derivatives as microtubule-targeted anticancer agents. Bioorg Med Chem 18(6):2089–2098. doi:10.1016/j.bmc.2010.02.012

    Article  PubMed  CAS  Google Scholar 

  • Won SJ, Cheng CT, Tsao LT, Weng JR, Ko HH, Wang JP, Lin CN (2005) Synthetic chalcones as potential anti-inflammatory and cancer chemopreventive agents. Eur J Med Chem 40(1):103–112. doi:10.1016/j.ejmech.2004.09.006

    Article  PubMed  CAS  Google Scholar 

  • Xue N, Yang X, Wu R, Chen J, He Q, Yang B, Lu X, Hu Y (2008) Synthesis and biological evaluation of imidazol-2-one derivatives as potential antitumor agents. Bioorg Med Chem 16(5):2550–2557. doi:10.1016/j.bmc.2007.11.048

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The author is deeply thankful to the staff members of the Department of Health and Human Services, National Cancer Institute (NCI), Bethesda, Maryland, USA, for carrying out the anticancer screening of the newly synthesized compounds.

Author information

Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt

    Ibrahim Chaaban, El Sayeda M. El Khawass, Mona A. Mahran, Heba A. Abd El Razik & Nehad S. El Salamouni

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia

    Mona A. Mahran

  3. Medical Biotechnology Department, Genetic Engineering and Biotechnology Research Institute (GEBRI), Borg El-Arab, Alexandria, Egypt

    Abeer E. Abdel Wahab

  4. City for Scientific Research and Technology Application (Previously Mubarak City for Scientific Research and Technology Application), Borg El-Arab, Alexandria, Egypt

    Abeer E. Abdel Wahab

Authors
  1. Ibrahim Chaaban
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. El Sayeda M. El Khawass
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mona A. Mahran
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Heba A. Abd El Razik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nehad S. El Salamouni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Abeer E. Abdel Wahab
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heba A. Abd El Razik.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chaaban, I., El Khawass, E.S.M., Mahran, M.A. et al. Synthesis and biological evaluation of novel hydroquinone dimethyl ethers as potential anticancer and antimicrobial agents. Med Chem Res 22, 3760–3778 (2013). https://doi.org/10.1007/s00044-012-0337-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-012-0337-y

Keywords

Search

Navigation