Novel Cytotoxic Oxopyridoindolizines: iso-Propyl-7,8,9-trichloro-6,7,8,9-tetrahydro-5-oxopyrido[2,3-a]-indolizine-10-carboxylates (OPIC)

Abstract

A series of eight new alkyl-7,8,9-trichloro-6,7,8,9-tetrahydro-5-oxopyrido[2,3-a]-indolizine-10-carboxylates (OPIC), analogues of camptothecin (CPT), were prepared in a one-pot reaction of 2,2'-bipyridine-3,3'-dicarboxylic acid (BPA) with a mixture of thionyl chloride/chlorine, followed by addition of the appropriate alcohol. This led to a mixture of OPIC compounds 3a-d, 4a-d and 3,3'-dialkoxycarbonyl-2,2'-bipyridines (BPE, 2a-d). The isopropyl OPIC 3c and its corresponding diastereoisomer 4c showed marked activity against three cancer cell lines compared to other analogs. These same diastereoisomers also displayed high cytotoxic activity against five leukemia cell lines, thus the presence of an isopropyl substituent on the carboxylic ester, as opposed to other alkyl substituents, appears to play a key role in the cytotoxic potency of this new class of compounds.

Antimicrobial Activity of Some Novel Armed Thiophene Derivatives and Petra/Osiris/Molinspiration (POM) Analyses

“…Of the most important program, Osiris is already available online [33] and very useful for its design/prediction of various activities. In our recent publications [34,35,36,37,38,39,40,41,42,43] on the drug design of various pharmacophore sites by using spiro-heterocyclic structures, we have predicted activity and/or inhibition with increasing success in two targets, Mycobacterium tuberculosis and HIV. This is done by using a combined electronic/structure docking procedure.…”

Computational evaluation and experimental in vitro antibacterial, antifungal and antiviral activity of bis-Schiff bases of isatin and its derivatives

“…Pharmacophore sites identification and then optimization (Anaflous et al, 2004;Ben Hadda et al, 2003Chohan et al, 2006;Hakkou et al, 2002;Houari et al, 2008) plays a major role in many steps of the drug discovery processes. A better understanding and modelling of the pharmacophore sites could greatly increase the efficiency for developing new efficient antibacterial (Anaflous et al, 2004;Ben Hadda et al, 2003Chohan et al, 2006;Hakkou et al, 2002;Houari et al, 2008), antitumoral (Zunino et al, 2002) and combined antitubercular/anti-HIV-1 drugs (Ben Hadda et al, 2005;Bennani et al, 2007).…”