Pharmaceutical Chemistry

Biography

Biography: Eslam EL-SAWY

Abstract

Resistance to conventional chemotherapy, leads to the need for development of novel safe and effective cancer therapies with new mechanism of action. Anti-angiogenic drugs are major example of such newly developed targeted therapeutics .In cancer drug development arena, coumarin-type compounds have been reported to bosses marked cytotoxic activities, in addition act as novel angiogenesis inhibitors. In this respect,a new series of coumarin derivatives was synthesized starting from 2-oxo-2H-coumarin-6-sulfonyl chloride (1), 6-nitro-2-oxo-2H-coumarin-3-sulfonyl chloride (10) and 6-amino coumarin-2-one (19). Reaction of 1 or 10 with 2-cyanoacetohydrazide, 2`-acetyl-2-cyanoacetohydrazide or 3-amino-5-pyrazolone afforded pyrazoline derivatives. While reaction of1 or 10 with malononitrile followed by reaction with hyadrazine hydrate, urea, thiourea or guanidine led to the formation of pyrazole and pyrimidine derivatives. On the other hand, compound 19 on reaction with VilsmeierHaack reagent yielded the corresponding aldehyde20. Compound 20 under reaction with chlorosulfonylisocyanate afforded N-chlorosulfonyl amid which cyclized to give pyranobenzothiazine derivative 25. The tested compounds 4, 5, 8, 12, 13 and 14 were non-cytotoxic against hepatocellular carcinoma cells (HepG2) using MMT. These non-cytotoxic compounds were evaluated as anti-angiogenicagent. Collectively, our results indicate that, coumarin molecules 4, 5, 8, 13 and 14 can be utilized as lead compounds to develop potential non-toxic angiogenesis inhibitors and small molecular ligands to target (HepG2), which was in concomitant with molecular docking results. 1-Acetyl-5-amino-4-(2-oxo-2H-chromene-6-sulfonyl)-1,2-dihydro-pyrazol-3-one (4) considered a promising anti-angiogenic agent, where it exhibited MMP-dependent anti-migratory activity and down regulated CD105.