Indolo[2,3-b]quinolines: The Lead compound Neocryp-tolepine and its synthetic Derivatives: from traditional usages to isolation, synthesis and biological activity

This thesis presents the work carried out during a six-month Erasmus traineeship at the Université de Reims Champagne-Ardenne, focused on the study and synthesis of indolo[2,3-b]quinoline derivatives. These compounds originate from Cryptolepis sanguinolenta, a West African medicinal plant traditionally used for treating malaria and infections. Among its alkaloids, Neocryptolepine has gained interest for its antimalarial, antiproliferative, antibacterial and antibiofilm properties, as well as for its ability to interact with DNA and topoisomerase II. The first part of the thesis outlines the biological relevance of indoloquinolines and their structure–activity relationships, highlighting how small structural modifications can markedly influence activity and selectivity. The experimental work focuses on synthesizing a small library of indoloquinoline analogues using a convergent strategy. The key step is a radical cascade reaction involving a Smiles rearrangement, followed by catalytic deprotection leading to intramolecular cyclisation and formation of the final tetracyclic core. Reaction conditions were optimized to improve yields and obtain several new intermediates and derivatives. The synthesized compounds are intended for future in vitro evaluation in combination with ciprofloxacin against Pseudomonas aeruginosa as part of an ongoing project exploring new antibiofilm approaches. Overall, the work combines natural-product-inspired drug discovery with modern synthetic methods, contributing useful building blocks and insights for the development of new indoloquinoline-based bioactive molecules.