Design, synthesis, and biological evaluation of a focused pyrrolo- and pyrido-quinazolinone natural products-templated library for anti-fungal and anthelmintic activities

Abstract

A focused pyrrolo- and pyrido-quinazoline natural products-templated library has been designed and synthesized using two novel synthetic approaches: an aza-Nazarov approach and a Dieckmann cyclization strategy. This privileged scaffold-based collection was screened against pathogenic fungi and parasitic helminths. Three compounds (23b, 25a, 13f) emerged as potent inhibitors of Candida auris adhesion, each causing more than 50 % inhibition at 10 μM, and two compounds (13k, 14h) displayed strong anthelmintic activity, demonstrating 7- to 28-fold enhanced activity against human hookworms relative to albendazole. These molecules represent promising leads for the design and synthesis of focused quinazolinone analogs to support SAR driven optimization against C. auris or helminth pathogens. Ongoing efforts aim to refine these bioactive leads by improving their pharmacokinetic and activity profiles through targeted structural modifications.