Synthesis and cytotoxic evaluation of some quinazolinone- 5-(4-chlorophenyl) 1, 3, 4-oxadiazole conjugates

Farshid Hassanzadeh , Hojjat Sadeghi-Aliabadi, Elham Jafari , Azadeh Sharifzadeh, Nasim Dana


1, 3, 4- Oxadiazoles and quinazolinones are privileged structures with extensive biological activities. On account of reported anticancer activity of them, in this study, a multi-step reaction procedure has been developed for the synthesis of some quinazolinone-1, 3, 4-oxadiazole derivatives. Reaction of the synthesized 3-amino-4(3H) quinazolinone derivatives with chloroacetyl chloride in the presence of dichloromethane/triethylamine yielded 2-chloro -N-(4-oxo-2-quinazolin3 (3H)-yl) acetamide derivatives as intermediate. Treatment of the resultants with 5- (4-chlorophenyl) 1, 3, 4-oxadiazole-2-thiol in dry acetone and potassium carbonate gave coupled derivatives of quinazolinone-1, 3, 4-oxadiazole. The cytotoxic effect of final compounds was tested against MCF-7 and HeLa cell lines using MTT assay. Compound 2-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-ylthio) N-(4-oxo-2-propylquinazolin)3(4H)acatamide 6a exhibited remarkable cytotoxic activity at 10 and 100 µM against HeLa cell line. The alteration of substituents on C2 of quinazolinone ring revealed that the introduction of propyl moeity improved cytotoxic activity against HeLa cell line.


Cytotoxicity; Quinazolinone; Oxadiazole.

Full Text:



Puthiyapurayil P, Poojary B, Chikkanna C, Buridipad SK. Design, synthesis and biological evaluation of a novel series of 1,3,4-oxadiazole bearing N-methyl-4-(trifluoromethyl)phenyl pyrazole moiety as cytotoxic agents. Eur J Med Chem. 2012;53:203-210.

Singh R, Chouhan A. Various approaches for synthesis 3, 4-oxadiazole derivative and their pharmacological activity. World J Pharm Pharm Sci. 2014;3(10):1474-1505.

Siddiqui SZ, Rehman A, Abbasi MA, Abbas N, Khan KM, Ashraf M, et al. Synthesis, characterization and biological screening of N-substituted derivatives of 5-benzyl-1,3,4-oxadiazole-2yl-2''-sulfanyl acetamide. Pak J Pharm. Sci. 2013;26(3):455-463.

Jafari E, Mohammadi T, Jahanian-Najafabadi A, Hassanzadeh F. Synthesis and antimicrobial evaluation of some 2,5 disubstituted 1,3,4-oxadiazole derivatives. Res Pharm Sci. 2017;12(4):330-336.

Kumar A, Gupta A, Kashaw V, Shukla G, Mishra V, Kashaw SK. Synthesis and anticancer evaluation of some novel 3-[5-(4-Substituted) Phenyl1,3,4-oxadiazole2yl-]-2-phenylquinazoline4(3H)-ones. Int J Pharm Pharm Sci. 2012;4(suppl 1):502-506.

de Oliveira CS, Lira BF, Barbosa-Filho JM, Lorenzo JG, de Athayde-Filho PF. Synthetic approaches and pharmacological activity of 1,3,4-oxadiazoles:a review of the literature from 2000-2012. Molecules. 2012,17(9):10192-10231.

Singh R, Chouhan A. Biological importance of 1, 3, 4-oxadiazole derivatives. IJABR. 2013;3(2):140-149.

Ramazani A, Khoobi M, Torkaman A, Nasrabadi FZ, Forootanfar H, Shakibaie M, et al. One-pot, four-component synthesis of novel cytotoxic agents1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines. Eur J Med Chem. 2014;78:151-156.

Noolvi MN, Patel HM, Bhardwaj V, Chauhan A. Synthesis and in vitro antitumor activity of substituted quinazoline and quinoxaline derivatives: search for anticancer agent. Eur J Med Chem. 2011;46(6):2327-2346.

Chawla A, Batra Ch. Recent advances of quinazolinone derivatives as marker for various biological activities. Int Res J Pharm. 2013;4(3): 49-58.

Khodarahmi GA, Rahmani Khajouei M, Hakimelahi GH, Abedi D, Jafari E, Hassanzadeh F. Antibacterial, antifungal and cytotoxic evaluation of some new 2, 3-disubstituted 4(3H)-quinazolinone derivatives. Res Pharm Sci. 2012;7(3):151-158.

Khodarahmi GA, Jafari E, Hakimelahi GH, Abedi D, Rahmani Khajouei M, Hassanzadeh F. Synthesis of some new quinazolinone derivatives and evaluation of their antimicrobial activities. Iran J Pharm Res. 2012;11(3):789-797.

Rezaee Nasab R, Mansourian M, Hassanzadeh F. Synthesis, antimicrobial evaluation and docking studies of some novel quinazolinone Schiff base derivatives. Res Pharm Sci. 2018;13(3):213-221.

Jafari E, Rahmani Khajouei M, Hassanzadeh F, Hakimelahi GH, Khodarahmi GA. Quinazolinone and quinazoline derivatives: recent structures with potent antimicrobial and cytotoxic activities. Res Pharm Sci. 2016;11(1):1-14.

Vaseghi G, Jafari E, Hassanzadeh F,Haghjooy-Javanmard Sh, Dana N, Rafi eian-Kopaei M. Cytotoxic evaluation of some fused pyridazino- and pyrrolo-quinazolinones derivatives on melanoma and prostate cell lines. Adv Biomed Res. 2017;6:76.

Sowjanya C, RamaBharathi V, Devi GK, Rajitha G. Synthesis and evaluation of some novel 3-[5-phenyl-1,3,4-oxadiazole-2-yl]-2(substitutedstyryl)-quinazoline-4(3H)-ones for antibacterial activity. J Chem Pharm Res. 2011;3(6):212-216.

Rajasekaran S, Gopalkrishna R. Synthesis and anti-denaturation activity of some substituted quinazolinone analogs. Int J Chem Tech Res. 2012;4(3):1207-1211.

Rajasekaran S, Gopalkrishna R. Synthesis, antibacterial and antioxidant activity of some 2, 3-susbtituted quinazolin-4(3H)-ones. Der Pharmacia Lett. 2012;4(2):470-474.

Qiao F, Yin Y, Shen YN, Wang SF, Sha S, Wu X, et al. Synthesis, molecular modeling, and biological evaluation of quinazoline derivatives containing the 1,3,4-oxadiazole scaffold as novel inhibitors of VEGFR. RSC Adv. 2015;5(26):19914-19923.

Dhani R. Analgesic activity of 3-[(5-substitued) - 1, 3, 4 oxadiazole-2-yl) methylamino]-2-methyl quinazolin-4(3h)-ones. Int J Anal Pharm Biomed Sci. 2012;1(4):30-33.

Alagarsamy V, Solomon VR, Sulthana MT, Vijay MS, Narendhar B. Design and synthesis of quinazolinyl acetamide for their analgesic and anti-inflammatory activities. Z Naturforsch. 2015;70(8):1-8.

Hassanzadeh F, Sadeghi-aliabadi H, Nikooei S, Jafari E, Vaseghi G. Synthesis and cytotoxic evaluation of some derivatives of triazole-quinazolinone hybrids. Res Pharm Sci. 2019;14(2):130-137.

Jafari E, Khodarahmi GA, Hakimelahi GH, Tsai FY, Hassanzadeh F. Synthesis of some new tricyclic 4(3H)-quinazolinone derivatives. Res Pharm Sci. 2011;6(2):93-100.

Bajaj S, Asati V, Singh J, Roy PP. 1,3,4-Oxadiazoles: an emerging scaffold to target growth factors,enzymes and kinases as anticancer agents. Eur J Med Chem. 2015;97:124-141.

Ouyang X, Piatnitski EL, Pattaropong V, Chen X, He HY, Kiselyov AS, et al. Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell line. Bioorg Med Chem Lett. 2006;16(5):1191-1196.

Zhang XM, Qiu M, Sun J, Zhang YB, Yang YS, Wang XL, et al. Synthesis, biological evaluation, and molecular docking studies of 1, 3,4-oxadiazole derivatives possessing 1,4-benzodioxan moiety as potential anticancer agents. Bioorg Med Chem. 2011;19(21):6518-6524.

Tiwari AK. Singh VK, Bajpai A, Shukla G, Singh S, Mishra AK. Synthesis and biological properties of 4-(3H)-quinazolone derivatives. Eur J Med Chem. 2007;42(9):1234-1238.

Ahmed MF, Belal A. Synthesis, characterization, and biological evaluation of new quinazolin-4-one derivatives hybridized with pyridine or pyran moiety. Res Chem Inter med. 2016;42(2):659-671.

Alafeefy AM, Ahmad R, Abdulla M, Eldehna WM, Al-Tamimi AM, Abdel-Aziz HA, et al. Development of certain new 2-substituted-quinazolin-4-ylaminobenzenesulfonamide as potential antitumor agents. Eur J Med Chem. 2016;109:247-253.

Taherian E, Khodarahmi G, Rahmani Khajouei M, Hassanzadeh F, Dana N. Synthesis and cytotoxic evaluation of novel quinozalinone derivatives with substituted benzimidazole in position 3. Res Pharm Sci, 2019; 14(3):247-254.


  • There are currently no refbacks.

Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.