Design and synthesis of a new class of cryptophycins based tubulin inhibitors

摘要: Tubulin binding compounds represent one of the most attractive targets for anticancer drug development. They broadly fall into two categories viz., tubulin polymerization inhibitors, which block microtubule growth and destabilize microtubules like vinca alkaloids cryptophycins, others, polymerize hyperstable forms represented by family taxanes. In this context, we aimed at design synthesis cryptophycins based macrocyclic depsipeptides, are synthetically more accessible, however have basic information to target tubulins establish structure activity relationship (SAR). Thus, a new class marocyclic depsipeptides with truncated epoxide chain were synthesized as potential inhibitors. The resultant lead analogues 15a 16a exhibited good anti-cancer activity, induced apoptosis, caused block/delay in cell cycle well significantly reduced expression α- β-tubulins. Molecular modelling studies show that bind same domain cryptophycins.