Structural, CSD, and computational studies of 6b, 11b-Dihydroxy-6b, 11-b-dihydro-7H-indeno[1,2-b]naptho[2,1-d]furan-7-one, a therapeutic potential small molecule

Abstract

Biochemical and pharmacological investigations carried out on the small molecule 6b, 11b-Dihydroxy-6b, 11-b-dihydro-7H-indeno[1,2-b]naptho[2,1-d]furan-7-one (DHFO) has shown that it is an analgesic, anti-inflammatory agent, and a dual 5-LOX/COX-2 inhibitor. DHFO is also a free-radical scavenger, a potent antioxidant, and an inhibitor of lipid peroxidation. We studied the structural properties of DHFO using single-crystal X-ray crystallography, Hirshfeld surfaces, and energy frameworks studies. Additionally, we also examined the conformational behavior of 29 molecular analogues of DHFO retrieved from the Cambridge Structural Database (CSD), which were similar to DHFO in flexibility, the effect of the substitution, and electrostatic interaction forces. Besides, we carried out the molecular docking studies to analyze the binding efficiency of DHFO with COX-1, COX-2, 5-LOX, and Cdc25B-cd (the catalytic domain of human Cdc25B phosphatase, which is identified as an arsenic reductase) proteins co-crystallized with standard drugs such as meloxicam. DHFO showed a better affinity with COX-2 than COX-1 and can potentially bind with CdC25B-cd protein. The drug-likeness of DHFO was also evaluated using Lipinski's rule, the SwissADME database, and DHFO possessed potential drug-likeness properties. In summary, the DHFO may potentially act as a multifunctional inhibitor by binding cyclooxygenase and arsenic binding proteins.