Solid-phase synthesis of new pyrrolobenzodiazepine-chalcone conjugates: DNA-binding affinity and anticancer activity.

A new class of C8-linked pyrrolo[2,1-c][1,4]benzodiazepine-chalcone conjugates have been prepared by employing a solid-phase synthetic protocol. In this strategy an intramolecular aza-Wittig reductive cyclization approach has been utilized. Interestingly, some of these molecules have shown enhanced DNA-binding affinity and promising anticancer activity on a large number of human cancer cell lines.

Synthesis of 1,2,3-triazole-linked pyrrolobenzodiazepine conjugates employing 'click' chemistry: DNA-binding affinity and anticancer activity.

1,2,3-Triazole based molecules are useful pharmacophores for several DNA-alkylating and cross-linking agents. A series of A/C8, C/C2 and A/C8-C/C2-linked 1,2,3-triazole-PBD conjugates have been synthesized by employing 'click' chemistry. These molecules have exhibited promising DNA-binding affinity and anticancer activity in selected human cancer cell lines.

Efficient solid-phase synthesis of a library of imidazo[1,2-a]pyridine-8-carboxamides.

A versatile method for the solid-phase synthesis of imidazo[1,2-a]pyridine-based derivatives, imidazo[1,2-a]pyridine-8-carboxamides, has been developed. They were obtained by treatment of the amino group of the polymer-bound 2-aminonicotinate with different alpha-haloketones, followed by halogenation at the 3-position of the polymer-bound imidazo[1,2-a]pyridine. The derived polymer-bound imidazo[1,2-a]pyridines 5, 6, and 7 were finally cleaved from the solid-support with an excess of primary or secondary amines. The final crude products were purified from excess amines by solid-supported liquid-liquid extraction (SLE).

Solid-phase synthesis of a library of pyrrolo[2,1-c][1,4]benzodiazepine-5,11-diones with potential antitubercular activity.

A versatile combinatorial approach was developed and utilized for the rapid synthesis of pyrrolo[2,1-c]-[1,4]benzodiazepine-5,11-dione (PBD-5,11-dione) libraries 10, 15, and 19 containing 210 compounds with varied substitutions in A, B, and C rings. The key aspect of the synthetic strategy includes Staudinger, intermolecular aza-Wittig reaction followed by imine reduction and base-mediated cyclative cleavage results in the formation of final resin-free compounds. This strategy provides a highly efficient and practical protocol for the parallel synthesis of PBD-5,11-diones on solid support. The modifications in the C-ring of the PBD scaffold produced three types of sublibraries. Reactions were monitored by FT-IR spectroscopy on the resin beads. Further, from a generated library of 210 compounds, 142 compounds have been selected and evaluated for in vitro activity against Mycobacterium tuberculosis, and some of these compounds have exhibited promising activity.

Recent advances in the solid-phase combinatorial synthetic strategies for the benzodiazepine based privileged structures.

Benzodiazepine based heterocycles can be prepared efficiently on solid-support by employing different approaches. In this review, an effort has been made to highlight academic and industrial examples of combinatorial synthesis for this type of heterocycles published in the last decade. Therefore, it describes synthetic strategies for the generation of benzodiazepine privileged structures employing the corresponding resin-bound substrates. Further, the most relevant biological properties of these heterocycles have also been incorporated.

Recent advances in the solid-phase combinatorial synthetic strategies for the quinoxaline, quinazoline and benzimidazole based privileged structures.

Quinoxaline, quinazoline and benzimidazole based templates have been synthesized on solid-support employing different methodologies. This review enlightens academic and industrial examples of combinatorial synthesis for this type of heterocycles that appeared in the literature in the last decade. Hence, some of the important synthetic strategies for the generation of quinoxaline, quinazoline and benzimidazole based privileged structures, and the important biological activities for these heterocycles have been highlighted. Further, benzothiadiazinone, thioxoquinazolinone, cinnoline and indazole are also examined in this review.

Synthesis and biological activity of fluoroquinolone-pyrrolo[2,1-c][1,4]benzodiazepine conjugates.

Fluoroquinolones have been synthesized and linked to DC-81 at C8 position through different alkyl chain spacers. These PBD conjugates have exhibited good DNA binding affinity, and a representative compound shows promising in vitro anticancer activity.