ABSTRACT
The facile synthesis of C-8 linked pyrrolobenzodiazepine-naphthalimide hybrid analogues is described. The compounds are prepared with varying degrees of linker length in order to probe the structural requirements for optimal in vitro anti-tumour activity. Some of these new hybrid compounds showed higher cytotoxic activity than the existing natural and synthetic pyrrolo[2,1-c][1,4]benzodiazepines.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Benzodiazepines/chemical synthesis , Benzodiazepines/pharmacology , Naphthalenes/chemical synthesis , Naphthalenes/pharmacology , Pyrroles/chemical synthesis , Pyrroles/pharmacology , Antineoplastic Agents/metabolism , Benzodiazepines/metabolism , DNA/metabolism , Drug Design , Drug Screening Assays, Antitumor , Humans , Lethal Dose 50 , Naphthalenes/metabolism , Pyrroles/metabolism , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Clinical use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with significant toxicity particularly in the gastrointestinal tract and kidney. Various approaches such as formulation co-administration (of agents to protect the stomach), chemical manipulation and synthesis of new safer anti-inflammatory drugs reported in the literature to overcome the toxicity of NSAIDs have been summarized. As far as synthesis of new more effective and safer anti-inflammatory drugs is concerned, we have reported recent findings in the area of synthesis of heterocyclic compounds such as pyrimidines, imidazole, benzimidazole, thiazole, thiazolidine, acridine, thiourea, alkanoic acid derivatives and other related heterocyclic compounds and their role as inflammation inhibitors.
