Novel antitumor indolizino[6,7-b]indoles with multiple modes of action: DNA cross-linking and topoisomerase I and II inhibition.

A series of bis(hydroxymethyl)indolizino[6,7-b]indoles and their bis(alkylcarbamates) were synthesized for antitumor studies. These agents were designed as hybrid molecules of β-carboline (topoisomerase inhibition moiety) and bis(hydroxymethyl)pyrrole (DNA cross-linking moiety). The preliminary antitumor studies indicated that these agents exhibited significant cytotoxicity against a variety of human tumor cells in vitro.

Evaluation of structurally diverse benzoazepines clubbed with coumarins as Mycobacterium tuberculosis agents.

Tuberculosis caused by Mycobacterium tuberculosis remains a leading cause of mortality worldwide into 21st century. In continuation with our anti-tuberculosis research programme, in this work, we have prepared molecularly diverse coumarins clubbed with benzothiazepines as well as its aza-analogues-benzodiazepines by molecular hybridization. The resulting compounds were screened for their M.

Synthesis and antitumor evaluation of novel benzo[d]pyrrolo[2,1-b]thiazole derivatives.

A series of novel 2,3-bis(hydroxymethyl)benzo[d]pyrrolo[2,1-b]thiazoles and their bis(alkylcarbamate) derivatives were synthesized starting from benzothiazole via reaction with dimethyl acetylenedicarboxylate (DMAD)/tetra-fluoro boric acid, catalytic hydrogenation, and alkylcarbamoylation. The anti-proliferative activity of these agents against human leukemia and various solid tumor cell growth in vitro was studied. The structure-activity relationship studies revealed that the bis(alkylcarbamates) derivatives are generally more cytotoxic than the corresponding bis(hydroxymethyl) congeners in inhibiting human lymphoblastic leukemia CCRF-CEM and various human solid tumor cell growth in culture.

Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates.

A series of N-mustard-quinazoline conjugates was synthesized and subjected to antitumor studies. The N-mustard pharmacophore was attached at the C-6 of the 4-anilinoquinazolines via a urea linker. To study the structure-activity relationships of these conjugates, various substituents were introduced to the C-4 anilino moiety.

Novel bifunctional alkylating agents, 5,10-dihydropyrrolo[1,2-b]isoquinoline derivatives, synthesis and biological activity.

A series of linear pyrrolo[1,2-b]isoquinoline derivatives was synthesized for antitumor evaluation. The preliminary antitumor studies reveal that both bis(hydroxymethyl) and their bis(alkylcarbamate) derivatives show significant antitumor activity in inhibiting various human tumor cell growth in vitro. 1,2-Bis(hydroxymethyl)-3-methyl-5,10-dihydropyrrolo[1,2-b]isoquinoline (20a) was selected for antitumor studies in animal models.