Synthesis, cytotoxic evaluation, and molecular docking studies of some new 1, 3, 4-oxadiazole-based compounds

Farshid Hassanzadeh , Elham Jafari , Mohammadreza Zarabi, Ghadamali Khodarahmi, Golnaz Vaseghi

Abstract


Background and purpose: Oxadiazole-derived compounds have been shown to have a wide range of pharmacological activities. 2, 5-Disubstituted 1, 3, 4-oxadiazole derivatives have occupied a specific place in the design of anti-proliferative agents. In the present work a series of 2, 5-disubstituted 1, 3, 4-oxadiazoles derivatives containing amide group has been synthesized via a two-step reaction.

Experimental approach: A mixture of substituted carboxylic acid derivatives, semicarbazide, and phosphorus oxychloride in reflux condition yielded 2-amino-5-aryl-1, 3, 4-oxadiazole derivatives. Acylation of the amino group of the resultant oxadiazole with 6-chloronicotinoyl chloride in dry tetrahydrofuran/pyridine afforded the final products. The synthesized molecules were docked in the active sites of the epidermal growth factor receptor tyrosine kinase domain (PDB: 1M17) crystal structure to study the possible interactions with the active site. Cytotoxic activities of final products against HeLa and MCF-7 cells were also assessed by MTT assay.

Findings/Results: Compounds IIb, IIc, and IIe had a considerable cytotoxic activity with IC50 values of 19.9, 35, and 25.1 µM, respectively against HeLa cells. The highest docking score was -7.89 kcal/mol for compound IIe.

Conclusion and implications: Compound IIe exhibited remarkable cytotoxic activity against the two tested cell lines particularly HeLa cells which was in accordance with the in silico ΔG bind result but further evaluations are necessary to prove these findings.


Keywords


Cytotoxicity; Molecular docking; Nicothionyl; Oxadiazole.

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Kumar A, Gupta A, Kashaw V, Shukla G, Mishra V, Kashaw SK. Syntheses and anticancer evaluation of some novel 3-[5-(4-substituted) phenyl-1,3,4-oxadiazole-2yl]-2-phenylquinazoline-4(3H)-ones. Int J Pharm Pharm Sci. 2012;4(1):502-506.

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

DOI: 10.1016/j.ejmech.2014.03.049.

Bondock S, Adel S, Etman HA, Badria FA. Synthesis and antitumor evaluation of some new 1,3,4-oxadiazole-based heterocycles. Eur J Med Chem. 2012;48:192-199.

DOI: 10.1016/j.ejmech.2011.12.013.

Ahsan MJ, Rathod VPS, Singh M, Sharma R, Jadav SS, Yasmin S, et al. Synthesis, anticancer and molecular docking studies of 2-(4-chlorophenyl)-5-aryl-1,3,4-oxadiazole analogues. Med Chem. 2013;3(4):294-297.

Singh R, Chouhan A. Various approaches for synthesis of 1,3,4-oxadiazole

derivatives and their pharmacological activity. World J Pharm Pharm Sci. 2014;3(10):1474-1505.

Pangal A, Shaikh JA. Various pharmacological aspects of 2,5-disubstituted 1,3,4-oxadiazole derivatives: a review. Res J Chem Sci. 2013;3(12):79-89.

Sharma S, Sharma PK, Kumar N, Dudhe R. A review: oxadiazole their chemistry and pharmacological potentials. Der Pharma Chemica. 2010;2(4):253-263.

Nagara J, Chaluvaraju KC, Niranjan MS, Kiran S. 1,3,4-Oxadiazole: a potent drug candidate with various pharmacological activities. Int J Pharm Pharm Sci. 2011;3(3):9­16.

Somani RR, Chiplunkar S, Vetale SP, Makhija DT, Shirodkar PY. Evaluation of apoptosis inducing activity of an oxadiazole based potential anticancer compound. Int J PharmTech Res. 2013;5(3):1233-1240.

Bhinder CK, Kaur A, Kaur A. Review: 1,3,4-oxadiazole as anticancer agent. Int J Pharm Res Bio Sci. 2014;3(4):457-479.

Sharma R, Kumar N, Yaday R. Chemistry and pharmacological importance of 1,3,4-oxadiazoles derivatives. J Chem. 2015;4(2):1-27.

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.

DOI: 10.1016/j.ejmech.2015.04.051.

Zachariah SM, Ramkumar M, George N, Ashif MS. A review on oxadiazole. Res J Pharm Bio Chem Sci. 2015;6(2):205-219.

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 lines. Bio Org Med Chem Lett. 2006;16:1191-1196.

DOI: 10.1016/j.bmcl.2005.11.094.

Adimule V, Medapa S, Jagadeesha AH, Kumar LS, Rao PK. Synthesis, characterization and cytotoxic evaluation of novel derivatives of 1,3,4-oxadiazole containing 5-phenyl thiophene moiety. J Pharm Bio Sci. 2014;9(5):42-48.

Biju CR, Ilango K. Docking investigation, synthesis and cytotoxic studies of substituted oxadiazole derivatives. Int J Pharm Pharm Sci. 2012;4(3):262-265.

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.

DOI: 10.4103/1735-5362.212051.

Deshmukh R, Jha AK, Thakur AS, Dewangan D. Synthesis and antibacterial activity of some 1,3,4-oxadiazole derivatives and their thione analogues. Int J Res Pharm Bio Med Sci. 2011;2(1):215-219.

Kumar CTK, Keshavayya J, Rajesh TN, Peethambar SK, Shoukat Ali AR. Synthesis, characterization, and biological activity of 5-phenyl-1,3,4-thiadiazole-2-amine incorporated azo dye derivatives. Org Chem Int. 2013;2013:1-7.

DOI: 10.1155/2013/370626.

Cressier D, Prouillac C, Hernandez P, Amourette C, Diserbo M, Lion C, et al. Synthesis, antioxidant properties and radioprotective effects of new benzothiazoles and thiadiazoles. Bioorg Med Chem. 2009;17(14):5275-5284.

DOI: 10.1016/j.bmc.2009.05.039.

Taher AT, Georgey HH, El-Subbagh HI. Novel 1,3,4-heterodiazole analogues: synthesis and in-vitro antitumor activity. Eur J Med Chem. 2012;47(1):445-451.

DOI: 10.1016/j.ejmech.2011.11.013.

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.

DOI: 10.4103/1735-5362.253360

Qin X, Li Z, Yang L, Liu P, Hu L, Zeng C, et al. Discovery of new [1,4]dioxino[2,3-f]quinazoline-based inhibitors of EGFR including the T790M/L858R mutant. Bioorg Med Chem. 2016;24(13):2871-2881.

DOI: 10.1016/j.bmc.2016.01.003.

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.

DOI: 10.4103/1735-5362.228942.

Sirous H, Zabihollahi R, Aghasadeghi MR, Sadat SM, Saghaie L, Fassihi A. Docking studies of some 5-hydroxypyridine-4-one derivatives: evaluation of integrase and ribonuclease H domain of reverse transcriptase as possible targets for anti-HIV-1 activity. Med Chem Res. 2015;24:2195-2212.

DOI: 10.1007/s00044-014-1289-1.

Ranjbar S, Edraki N, Khoshneviszadeh M, Foroumadi A, Miri R, et al. Design, synthesis, cytotoxicity evaluation and docking studies of 1,2,4-triazine derivatives bearing different arylidene-hydrazinyl moieties as potential mTOR inhibitors. Res Pharm Sci. 2018;13(1):1-11.

DOI: 10.4103/1735-5362.220962.

Niu P, Kang J, Tian X, Song L, Liu H, Wu J, et al. Synthesis of 2-amino-1,3,4-oxadiazoles and 2-amino-1,3,4-thiadiazoles via sequential condensation and I2-mediated oxidative C-O/C-S bond formation. J Org Chem. 2015;80(2):1018-1024.

DOI: 10.1021/jo502518c.

Tu G, Yan Y, Chen X, Lv Q, Wang J, Li S. Synthesis and antiproliferative assay of 1,3,4-oxadiazole and 1,2,4-triazole derivatives in cancer cells. Drug Discov Ther. 2013;7(2):58-65.

Oliveira CS, Lira BF, Barbosa-Filho JM, Lorenzo JGF, 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.

DOI: 10.3390/molecules170910192.

Sun J, Zhu H, Yang ZM, Zhu HL. Synthesis, molecular modeling and biological evaluation of 2-aminomethyl-5-(quinolin-2-yl)-1,3,4-oxadiazole-2(3H)-thione quinolone derivatives as novel anticancer agent. Eur J Med Chem. 2013;60:23-28.

DOI: 10.1016/j.ejmech.2012.11.039.

Hassanzadeh F, Sadeghi-Aliabadi H, Jafari E, Sharifzadeh A, Dana N. Synthesis and cytotoxic valuation of some quinazolinone-5-(4-chlorophenyl) 1,3,4-oxadiazole conjugates. Res Pharm Sci. 2019;14(5):408-413.

DOI: 10.4103/1735-5362.268201.


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