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Molecules 2002, 7(8), 628-640; doi:10.3390/70800628
Article

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

1, 2, 3, 4, 4, 5, 5, 5 and 4,5,*
1 Oncologia Sperimentale B, Instituto Nationale per lo Studio e la Cura dei Tumori, Via Venezian, 20133 Milano, Italy 2 Department of Chemistry and Biochemistry, 1 University Plaza, Long Island University, Brooklyn, NY 11201, USA 3 Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK 4 Department of Chemistry, Sciences Faculty of D'Har Elmehraz, Fès 30000, Morocco 5 Department of Chemistry, Sciences Faculty of Oujda, Oujda 60000, Morocco
* Author to whom correspondence should be addressed.
Received: 16 May 2002 / Revised: 5 August 2002 / Accepted: 5 August 2002 / Published: 31 August 2002
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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.
Keywords: Oxopyridopyndolizine carboxylate (OPIC); Cycloacylation; Camptothecin; Cancer; Chlorination; N-ligands Oxopyridopyndolizine carboxylate (OPIC); Cycloacylation; Camptothecin; Cancer; Chlorination; N-ligands
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Zunino, F.; Kotchevar, A.T.; Waring, M.; Daoudi, M.; Larbi, N.B.; Mimouni, M.; Sam, N.; Zahidi, A.; Ben-Hadda, T. Novel Cytotoxic Oxopyridoindolizines: iso-Propyl-7,8,9-trichloro-6,7,8,9-tetrahydro-5-oxopyrido[2,3-a]-indolizine-10-carboxylates (OPIC). Molecules 2002, 7, 628-640.

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