This paper reports on their design, synthesis, and testing of quinoline-3-carboxamides containing sulfonamide moieties, for potential ALK and ROS1 inhibitory activities for the treatment of non-small cell lung cancer (NSCLC). Lead compounds were identified through computational screening carried out using DrugRep Web Server based on the stability and the ability of these lead compounds to interact with receptor ATP-binding sites. Optimization of structure was necessary to enhance selectivity, lipophilicity, and ADMET properties by improving heterocyclic cores' configurations, substituents, and functional groups. It is established that 2-chloro-N-(4-hydroxyphenyl) quinoline-3-carboxamide has substantial potential as an inhibitor supported by pharamophore design. Therefore, the synthesis of ten derivatives was carried out with melting points established between 178 and 208 °C; while the Rf values lie within 0.48 and 0.60. They were purified to the high end with their response at the IR, ¹H NMR, and HRMS levels. Functional groups such as -OH, -Cl, and sulfonamide could now be incorporated for increased ALK and ROS1 kinase domain-binding. The synthesis of CQCS3 compound (90%) has shown that sulfonamide, too, has an occurrence in kinase binding with the highest yield and ALK-ROS1 kinase binding potential. These observations indicate quinoline-based derivatives might exhibit pertinent interest in precision oncology interventions for NSCLC treatments.
Keywords: Quinoline derivatives, ALK inhibitors, ROS1 inhibitors, NSCLC, Sulfonamide, Kinase inhibitors, Drug design, Virtual screening, Computational pharmacology, Precision oncology.
How to cite this article: Kurkute D, Lokhande R, Bhagat B, Hapse S, Shinde K, Ramteke K, Receptor-Based Virtual Screening and Synthesis of Dual Inhibitors Targeting Alk and Ros1 Kinases in Lung Cancer. Int J Drug Deliv Technol. 2025;15(4): 1666-1676, DOI: 10.25258/ijddt.15.4.18