A new route to thiazolo quinazoline derivatives and novel synthesis of pyrido, pyrimidoquinazoline as potential anticancer agents

In this study, one- pot three- components synthesis of thiazoloquinazoline 7, 9 using Gewald synthesis (Scheme 1). The synthesis of novel pyridoquinazoline 13a,c obtained via Michael addition of cyanomethylene to polarized exocyclic double bond of pyrimidinethione 1 (Scheme 2). Conjugate addition of imino group to benzylidene cyanoacetamide derivatives 14 b. Followed by intramolcular cyclization furnished thioxopyrimidopyrimidine 18 ( Scheme 3), In contrast, thiazinoquinazoline 21 obtained via cyclo-addition of bezylidene derivatives with compound 1 (Scheme 3). Biological property of the prepared molecules by cell cycle arrest was using compounds pyrido and pyrimidoquinazoline were selected for further antitumor activity evaluation against prostate cancer cell line of human ( PC3), (MDA-MB231) and cancer (HeLa). These agents showed 55–85% tumor suppression with low toxicity (5–8% body-weight changes). The inhibitory effects on cell proliferation were shown by conc. Dependent dependence by (20--100) lg/mL. Also, compound pyrimidoquinazoline the highest inhibitory activity was recorded.