Sustainable and innovative strategies for the discovery of new therapeutic agents

During my PhD, I integrated green chemistry principles to develop sustainable and efficient methods for synthesizing biologically active compounds. In collaboration with Nerviano Medical Sciences, I focused on metal-free visible-light photocatalysis to enable radical coupling reactions: Synthesis of a-halocarbonyl derivatives via a Giese-type photoredox process, yielding intermediates converted into amino esters, heterocycles, and cinnamic derivatives. This strategy facilitated the synthesis of pharmacologically relevant compounds such as ilepcimide (anticonvulsant), amiloxylate (photoprotective), and piperlongumine (anticancer agent). Phptocatalytic Giese-type protocol for N-t-Bu-TZD: I developed a mild, metal-free method coupling N-tert-butylthiazolidindione-based olefins with organoborates or carboxylic acids, demonstrating broad applicability and enabling the synthesis of anti¬diabetic glitazones like azemiglitazone and pioglitazone. Concurrently, I explored novel strategies to target indoleamine 2,3-dioxygenase 1 (IDO1) in cancer immunotherapy, overcoming limitations of conventional inhibitors through three approaches: Apo-IDOI inhibitors: I optimized VS-13 through SAR/SPR studies, incorporating bioisosteric modifications (H/D, H/F) and structural refinements to enhance pharmacokinetics, leading to an improved analogue.