Synthesis and cytotoxic evaluation of some new 3-(2-(2-phenylthiazol-4-yl) ethyl)-quinazolin-4(3H) one derivatives with potential anticancer effects

Leila Hosseinzadeh, Alireza Aliabadi, Mohsen Rahnama, Hamid Mir Mohammad Sadeghi, Marzieh Rahmani Khajouei

Abstract


Quinazolinones are a group of heterocyclic compounds that have important biological activities such as cytotoxicity, anti-bacterial, and anti-fungal effects. Thiazole-containing compounds have also many biological effects including antitumor, antibacterial, anti-inflammatory, and analgesic activities. Due to significant cytotoxic effects of both quinazoline and thiazole derivatives, in this work a group of quinazolinone-thiazol hybrids were prepared and their cytotoxic effects on three cell lines were evaluated using MTT assay. Compounds A3, A2, B4, and A1 showed highest cytotoxic activities against PC3 cell line. Compounds A3, A5, and A2 were most active against MCF-7 and A3, A5, and A6 showed good cytotoxic effect on HT-29 cell line. According to the results, A3 efficiently inhibited all cell growth tested in a dose dependent manner. The IC50 of A3 was 10 M, 10


Keywords


Quinazolinone; Thiazole; Cytotoxic

Full Text:

PDF

References


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.

Solomon VR, Hu C, Lee H. Design and synthesis of anti-breast cancer agents from 4-piperazinylquinoline: a hybrid pharmacophore approach. Bioorg Med Chem. 2010;18(4):1563-1572.

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.

Mhaske SB, Argade NP. The chemistry of recently isolated naturally occurring quinazolinone alkaloids. Tetrahedron. 2006;62(42):9787-9826.

Gursoy A, Unal B, Karali N, Otuk G. Synthesis, characterization and primaryantimicrobial activity evaluation of 3-Phenyl-6- methyl-4-(3H)-quinazolinone-2-yl-mercaptoacetic acid arylidene-hydrazides. Turk J Chem. 2005;29(3):233-245.

Mourad AFE, Aly AA, Farag HH, Beshr EA. Microwave assited synthesis of triazolo-quinazolinones and benzimidazoqina-zolinones. Beilstein J Org Chem. 2007;3(11):1-5.

Zhou Y, Murphy DE, Sun Z, Gregor VE. Novel parallel synthesis of N-(4-oxo-2-substituted-4-H-quinazolin-3-yl)-substituted sulfonamides. Tetrahedron Lett. 2004;45(43):8049-8051.

Dinakaran M, Selvam P, DeClercq E, Sridhar SK. Synthesis, antiviral and cytotoxic activity of 6- bromo-2, 3-disubstituted-4 (3H)-quinazolinones. Biol Pharm Bull. 2003;26(9):1278-1282.

Raghavendra NM, Thampi P, Gurubasavarajaswamy PM, Sriram D. Synthesis and antimicrobial activities of some novel substituted 2-Imidazolyl-N-(4-oxoquinazolin-3 (4H)-yl)-acetamides. Chem Pharm Bull (Tokyo). 2007;55(11):1615-1619.

Laddha S, Wadodkar SG, Meghal SK. Studies on some biologically active substituted 4(3H)-quinazolinones. Part 1. Synthesis, characterization and anti-inflammatory-antimicrobial activity of 6, 8-disubstituted 2-phenyl-3-[substituted-benzothiazol-2-yl]-4(3H)-quinazolinones. Arkivoc. 2006;11:1-20.

Pandeya SN, Sriram D, Nath G, De Clercq E. Synthesis, antibacterial, antifungal and anti-HIV evaluation of Schiff and Mannich bases of isatin derivatives with 3-amino-2-methylmercapto quinazolin-4 (3H)-one. Pharm Acta Helv. 1999;74(1):11-17.

Nanda AK, Ganguli S, Chakraborty R. Antibacterial activity of some 3-(Arylideneamino)-2-phenylquinazoline-4(3H)-ones: synthesis and preliminary QSAR studies. Molecules. 2007;12(10):2413-2426.

Philipova I, Dobrikov G, Krumova K, Kaneti J. Convenient synthesis of some 2 substituted 4 (3H) quinazolinone derivatives. J Heterocyclic Chem. 2006;43:1057-1063.

Gürsoy A, Karali N. Synthesis and primary cytotoxicity evaluation of 3-[[(3-phenyl-4 (3H)- quinazolinone-2-yl) mercaptoacetyl] hydrazono]-1H-2-indolinones. Eur J Med Chem. 2003;38(6):633-643.

Ghabrial SS, Gaber HM. Dipolar cycloaddition reactions with quinazolinones: a new route for the synthesis of several annelated pyrrolo and pyridazino quinazoline derivatives. Molecules. 2003;8(5):401-410.

Refaie FM, Esmat AY, Gawad SM, Ibrahim AM, Mohamed MA. The antihyperlipidemic activities of 4 (3H) quinazolinone and two halogenated derivatives in rats. Lipids Health Dis. 2005;4:22.

Shcherbakova I, Balandrin MF, Fox J, Ghatak A, Heaton WL, Conklin RL. 3H-Quinazolin-4-ones as a new calcilytic template for the potential treatment of osteoporosis. Bioorg Med Chem Lett. 2005;15(6):1557-1560.

Liu JF, Lee J, Dalton AM, Bi G, Yu L, Baldino CM, et al. Microwave-assisted one-pot synthesis of 2, 3- disubstituted 3H-quinazolin-4-ones. Tetrahedron Lett. 2005;46:1241-1244.

Piller LB, Davis BR, Cutler JA, Cushman WC, Wright Jr JT, Williamson JD, et al. Validation of heart failure events in the antihypertensive and lipid lowering treatment to prevent heart attack trial (ALLHAT) participants assigned to doxazosin and chlorthalidone. Curr Control Trials Cardiovasc Med. 2002;3(1):10.

Akazome M, Yamamoto J, Kondo T, Watanabe Y. Palladium complex-catalyzed intermolecular reductive N-heterocyclization: novel synthesis of quinazoline derivatives from 2-nitrobenzaldehyde or 2-nitrophenyl ketones with formamide. J Organomet Chem. 1995;494(1-2):229-233.

Al-Omary FA, Abou-zeid LA, Nagi MN, Habib el-SE, Abdel-Aziz AA, El-Azab AS, et al. Nonclassical 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.

Cao SL, Feng YP, Jiang YY, Liu SY, Ding GY, Li RT. Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains. Bioorg Med Chem Lett. 2005;15(7):1915-1917.

Bharti SK, Nath G, Tilak R, Singh SK. Synthesis, antibacterial and anti-fungal activities of some novel Schiff bases containing 2, 4-disubstituted thiazole ring. Eur J Med Chem. 2010;45(2):651-660.

Khalil AM, Berghot MA, Gouda MA. Synthesis and antibacterial activity of some new thiazole and thiophene derivatives. Eur J Med Chem. 2009;44(11):4434-4440.

Pandeya SN, Sriram D, Nath G, DeClercq E. Synthesis, antibacterial, antifungal and anti-HIV activities of schiff and mannich bases derived from isatin derivatives and N-[4-(4'-chlorophenyl) thiazol- 2-yl] thiosemicarbazide. Eur J Pharm Sci. 1999;9(1):25-31.

Cukurovali A, Yilmaz I, Gur S, Kazaz C. Synthesis, antibacterial and antifungal activity of some new thiazolylhydrazone derivatives containing 3-substituted cyclobutane ring. Eur J Med Chem. 2006;41(2):201-207.

Li J, Xu Z, Tan M, Su W, Gong XG. 3-(4-(Benzo[d]thiazol-2-yl)-1-phenyl-1H-pyrazol-3-yl) phenyl acetate induced Hep G2 cell apoptosis through a ROS-mediated pathway. Chem Biol Interact. 2010;183(3):341-348.

Luo Y, Xiao F, Qian S, Lu W, Yang B. Synthesis and in vitro cytotoxic evaluation of some thiazolylbenzimidazole derivatives. Eur J Med Chem. 2011;46(1):417-422.

Saghaie L, Sadeghi-Aliabadi H, Ashaehshoar M. Synthesis, analysis and cytotoxic evaluation of some hydroxypyridinone derivatives on HeLa and K562 cell lines. Res Pharm Sci. 2013;8(3):185-195.


Refbacks

  • There are currently no refbacks.


Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

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.