SYNTHESIS OF NEW QUINAZOLINONE-BASED CONJUGATES AND IN VITRO CYTOTOXIC EVALUATION
Keywords:quinazolinone, cytotoxic, conjugate, cancer
AbstractA series of new quinazolione derivatives containing a conjugate sytem 13 a-l were synthesized via a three step-procedure. The first step is the condensation of 5-hydroxyanthranilic acid (10) at 160oC for 2 h to afford the intermediate 11 in high yield. This intermediate was then reacted with n-butylamin in acetic acid at 160oC for 14 h to give 12 in 92%. Finally, the reaction of 12 with different aldehydes in acetic acid at 140oC for 14h furnished new conjugates 13a-l in 62-81%. The bioassay results showed that several compounds displayed cytotoxic effect against two cell lines including HepG-2 and SKLu-1 in which 13h exhibited the strongest cytotoxic effect against SKLu-1 with IC50 value of 5.05 µg/mL.
World Health Organization, International Agency for Research on Cancer (IARC) – Global cancer rates could increase by 50% to 15 million by 2020- World cancer report (2003).
Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018.
Nikolaou M., Pavlovpulou A., Georgakilas A. G., Kyrodioms E., The challenge of drug resistance in cancer treatment: a current overview. Clin. Exp. Metastasis. 35 (2018) 309-318.
Lamberth, C. & Dinges, J. Bioactive Heterocyclic Compound Classes: Pharmaceuticals and Agrochemicals (Wiley-VCH, 2012).
Connolly D. J., Cusack D., O’Sullivan T. P., Guiry P. J. Synthesis of quinazoliones and quinazolines, Tetrahedron 61 (2005) 10153–10202.
Rajput R., Mishar A. P. A review on biological activity of quinazoliones. Acadamic Sciences. 4 (2012) 66–70.
Yadav M. R., Naik P. P., Gandhi H. P., Chauhan B. S., Giridhar R. Design and synthesis of 6,7-dimethoxyquinazoline analogs as multi-targeted ligands for α1- and AII-receptors antagonism. Bioorg. Med. Chem. Lett. 23 (2013) 3959–3966.
Hameed A., Al-Rashida M., Uroos M., Ali S. A., Arshia., Ishtiaq M., Khan K. M. Quinazoline and quinazolinone as important medicinal scaffolds: a comparative patent review (2011–2016)- Expert Opin. Ther. Pat. 28 (2018) 281-29.
Selvam T. P, Kumar P. V. Quinazoline marketed drugs. Res Pharm. 1 (2015) 1-121.
Abida P. N, Arpanarana M. An updated review: newer quinazoline derivatives under clinical trial. Int J Pharm Biol Sci Arch. 2 (2011)1651–1657.
Bouley R., Ding, D., Peng, Z., Bastian, M., Lastochkin, E., Song W., Suckow, M. A., Schroeder V. A., Wolter W. R., Mobashery S., Chang M. Structure−activity relationship for the 4(3H) quinazolinone antibacterials. J. Med. Chem. 59 (2016) 5011−5021.
Scudiero D. A., Shoemaker R. H., Paull K. D., Monks A., Tierney S., Nofziger T. H.,
Currens M. J., Seniff D., Boyd M. - Feasibility of drug screening with panels of human
tumor cell lines using a microculture tetrazolium assay, Cancer Res. 48 (1988) 4827–
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