ABSTRACT
In the last decade, quinazoline has been one of the most explored scaffolds by researchers around the globe in medicinal chemistry. Its unique structural features provide a wide range of substitutions for nitrogen and carbonyl groups. In the current situation of COVID-19, hydroxychloroquine, an antimalarial drug of the quinoline category, was used for the treatment of severe infections. Various substitution patterns, hybrids, and conjugates of quinazoline have been developed and studied for various pharmacological activities like anticancer, anti-inflammatory, antimalarial, antitubercular, etc. The scaffold can be considered a potential molecule for various pharmacological activities, especially antimicrobial and anti-hypertensive. This review article aims to study the physicochemical properties, chemistry, and pharmacological profile of quinazoline.
Subject(s)
Anti-Infective Agents , Antimalarials , Antineoplastic Agents , COVID-19 , Humans , Quinazolines/pharmacology , Quinazolines/chemistry , Anti-Inflammatory Agents/chemistry , Anti-Infective Agents/chemistry , Antimalarials/pharmacology , Antineoplastic Agents/chemistryABSTRACT
Sunitinib is a potent anti-cancer scaffold that acts as a VEGFR-2 inhibitor. Although the scaffold exhibits potent anti-cancer activity, it is cardiotoxic and also induces hypothyroidism. The current research aims to optimize the Sunitinib for cardio-toxicity and thyro-toxicity by scaffold hopping approach using the admetSAR server. The server has optimized the physico-chemical properties of Sunitinib, which were contributing to the cardiotoxicity and thyro-toxicity. The library of the optimized compounds was further screened by the molecular docking studies and results were validated by the MD simulation and DFT analysis for VEGFR-2 inhibition. Compounds 163 and 432 exhibited the highest affinity to VEGFR-2 receptor with minimal cardiotoxicity and thyro-toxicity. These two compounds could be the starting point for the further discovery of angiogenic inhibitors. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-022-00125-1.
