Abul Bashar Ripon Khalipha1,2*, Md. Solayman Hossain1, Abdullah Al Shamsh Prottay1, Musfiqur Rahman Sakib1
1Department of Pharmacy, Life Science Faculty, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj 8100, Bangladesh
2Evergreen Scientific Research Centre, Gopalganj 8100, Bangladesh
In this study, we analyzed and summarized various bioactive compounds as a source of anticancer agents to determine the pharmacological activity of L. glutinosa (a bioactive chromone alkaloid) and to develop new chemical compounds that target Tumor necrosis factor ligand superfamily member 14 (TNFRSF6B) for cancer treatment. Significant anticancer, anti-inflammatory, gastro protective, insecticidal, and lipid-lowering activity is exhibited by L. glutinosa. One significant L. glutinosa analogs, boldine showed anticancer activity against 3K51, 4J6G, 4KGG, 3MHD, and 4MSV, are in clinical trials. Molecular docking analysis revealed that 4MSV is the best protein with which boldine interacts efficiently (-10.3 kcal/mol). Two boldine derivatives [N-methyldibenzo [de, g] quinoline ring-substituted compound (A) and N-methyl dibenzo [de, g] quinoline ring-substituted compound (B)] inhibit 4MSV protein considerably with binding affinity values of -11.5 kcal/mol and -11.00 kcal/mol, respectively. Additionally, Compound (D) with an N-Fluro-dibenzo[de,g]quinoline ring replaced possesses a high affinity for all TNFRSF6B proteins. Quantum mechanical calculations at the B3LYP/6-31G (d, p) level of theory revealed the charge distribution, dipole moment, and thermodynamic properties of boldine and modified medicines. Additionally, in silico pharmacokinetic studies projected that the changed compounds (A), (B), and (C) would exhibit significantly increased hydrophobicity, oral bioavailability, and plasma protein binding (D). Additionally, these molecules cross the blood-brain barrier, but the parent medication does not. Thus, the 4MSV protein may be a potential target for compounds (A) and (B), while the 3K51, 4J6G, and 4KGG proteins may be a target for compound (C) (D). Chemical synthesis and in vivo testing on a variety of cancer cells are necessary to determine these boldine analogs’ potential.