Synthesis and cytotoxic evaluation of some derivatives of triazole-quinazolinone hybrids

Farshid Hassanzadeh , Hojjat Sadeghi-aliabadi1, Shadan Nikooei, Elham Jafari, Golnaz Vaseghi

Abstract


Triazoles and quinazolinones are important heterocyclic structures with diverse biological properties including cytotoxic, antibacterial, antifungal and anticonvulsant activities. Due to valuable cytotoxic effects of both triazole and quinazoline derivatives, in this study a series of quinazolinone-triazole hybrids were synthesized in a multiple-step reaction procedure. 3-Amino-quinazolinone derivatives were treated with chloroacetyl chloride in the presence of dichloromethane/triethylamine to afford 2-chloro -N-(4-oxo-2-quinazolin3 (3H)-yl) acetamide derivatives. The reaction of resultants with 4-mehyl-4-H-1, 2, 4-triazole-3-thiol in dry acetone and potassium carbonate led to the formation of final products. Synthesized compounds were evaluated for their cytotoxic effects against MCF-7 and Hela cell lines using MTT colorimetric assay. Amongst tested compounds, 6a showed the highest cytotoxic activity against MCF7 cell line at all tested concentrations while compounds 6b and 6c indicated mild cytotoxic effects against Hela cell line at highest tested concentration reducing cell viability about 40%. The IC50 values of tested compounds revealed that the MCF-7 is more susceptible to the compound 6a.


Keywords


Cytotoxicity; Hybrid; Quinazolinone; Triazole.

Full Text:

PDF

References


Akbarzadeh T, Noushini S, Taban S, Mahdavi M, Khoshneviszadeh M, Saeedi M, Saeed Emami S, et al. Synthesis and cytotoxic activity of novel poly-substituted imidazo[2,1-c][1,2,4]triazin-6-amines. Mol Divers. 2015;19(2):273-281.

Hassanzadeh F, Jafari E, Hakimelahi GH, Rahmani Khajouei M, Jalali M, Khodarahmi GA. Antibacterial, antifungal and cytotoxic evaluation of some new quinazolinone derivatives. Res Pharm Sci. 2012;7(2):87-94.

Hassanzadeh F, Rahmani Khajouei M, Hakimelahi GH, Jafari E, Khodarahmi GA. Synthesis of some new 2,3-disubstituted-4(3H)quinazolinone derivatives. Res Pharm Sci. 2012;7(1):23-30.

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.

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 GH, Jafari E, Hakimelahi GH, Abedi D, Rahmani Khajouei M, Hassanzadeh F. Synthesis of some new quinazolinone derivatives and evaluation of their antimicrobial activities. Iranian 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 S, 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.

Abbot V, Sharma P, Dhiman S, Noolvi MN, Patel HM, Bhardwaj V. Small hybrid heteroaromatics: resourceful biological tools in cancer research. RSC Adv. 2017;7:28313-28349.

Shneine JK, Alaraji YH. Chemistry of 1, 2, 4-triazole: a review article. Int J Sci Res. 2016;5(3):1411-1423.

Ali KA, Ragab EA, Farghaly TA, Abdalla MM. Synthesis of new functionalized 3-substituted [1,2,4]triazolo [4,3-a]pyrimidine derivatives :potential antihypertensive agents. Acta Pol Pharm. 2011;68(2):237-247.

Kumar R, Yar MS, Chaturvedi S, Srivastava A. Triazole as pharmaceuticals potentials. Int J Pharmtech Res. 2013,5(4):1844-1869.

Asif M. Recent advancement of potentially significant Triazole derivatives. Discovery Chem, 2015;1(1):18-32.

Nazeer A, Parveen N, Aslam S, Ain Khan M, Munawar MA. Synthesis and antibacterial activity of 2-phenyl-5-aryl-4, 5, 6, 7, 8, 9- hexahydro- 1,2.4-triazolo[1,5-A] quinazolines. AFINIDAD. 2013;70(563):220-225.

Krastina G, Ravina I, Mierina I, Zicane D, Turks M, Tetere Z, et al. Synthesis of novel quinazolinone-1,2,3-triazole conjugates. J Chem Pharm Res. 2014,6(12):6-14

Ouahrouch A, Taourirte M, Engels JW, Benjelloun S, Lazrek HB. Synthesis of new 1,2,3-triazol-4-yl-quinazoline nucleoside and acyclonucleoside analogues. Molecules. 2014:19:3638-3653.

Atia AJKh, Al-Mufrgeiy SS. Synthesis and antibacterial activities of new3-amino-2-methyl-quinazolin-4 (3h)-one derivative. American J Chem. 2012,2(3):150-156.

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.

Abbas SE, Awadallah FM, Ibrahin NA, Said EG, Kamel GM. New quinazolinone-pyrimidine hybrids: synthesis, anti-inflammatory, and ulcerogenicity studies. E J Med Chem. 2012;53:141-149.

Marzaro G, Guiotto A, Chilin A. Quinazoline derivatives as potential anticancer agents: apatent review (2007 - 2010). Expert Opin Ther Pat. 2012:22(3):223-252.

Raffa D, Edler MC, Daidone G, Maggio B, Merickech M, Plescia S, et al. Synthesis, cytotoxicity, and inhibitory effects on tubulin polymerization of a new 3-heterocyclo substituted 2-styrylquinazolinones. Eur J Med Chem. 2004;39(4):299-304.

Xia Y, Yang ZY, Hour MJ, Kuo SC, Xia P, Bastow KF, et al. Antitumor agents. Part 204: synthesis and biological evaluation of substituted 2-aryl quinazolinones. Bioorg Med Chem Lett. 2001;11(9):1193-1196.

Al-Obaid AM, Abdel-Hamide SG, El-Kashef HA, Abdel-Aziz AM, El-Azab AS, Al-Khamees HA, et al. Substituted quinazolines, part 3. Synthesis, invitro antitumor activity and molecular modelingstudy of certain 2-thieno-4(3H)-quinazolinone analogs. Eur J Med Chem. 2009;44(6):2379-2391.

Al-Omary FA, Abou-zeid LA, Nagi MN, Habib ESE, Abdel-Aziz AA, El-Azab AS, et al. Non-classical antifolates. Part 2: synthesis, biological evaluation,and molecular modeling study of some new 2,6- substituted-quinazolin-4-ones. Bioorg Med Chem. 2010;18(8):2849-2863.

Hosseinzadeh L, Aliabadi A, Kalantari M, Mostafavi A, Rahmani Khajouei M. Synthesis and cytotoxicity evaluation of some new 6-nitro derivatives of thiazole-containing 4-(3H)-quinazolinone. Res Pharm Sci. 2016;11(3):210-218.

Singhal N, Sharma PK, Dudhe R, Kumar N. Recent advancement of triazole derivatives and their biological significance. J Chem Pharm Res. 2011;3(2):126-133.

Safavi M, Ashtari A, Khalili F, Mirfazli SS, Saeedi M, Ardestani SK, et al. Novel quinazolin-4(3H)-one linked to 1,2,3-triazoles: synthesis and anticancer activity. Chem Biol Drug Des. 2018;92(1):1373-1381.

Sahoo S, Patwari KP, Kumar MCB, Settyd CM. Synthesis and biological activity of certain mannich bases derivatives from 1, 2, 4-triazoles. Iranian J Pharm Sci. 2013;9(4):51-60.

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

Kamel MM, Zaghary WA, Al-wabli RI, Anwar MM. Synthetic approaches and potential bioactivity of different functionalized quinazoline and quinazolinone scaffolds. Egyptian Pharm J. 2016;15(3):98-131.


Refbacks

  • There are currently no refbacks.


Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported 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.