Identification of anti-cyanobacterial leads targeting carbonic anhydrase from phytochemical database using in silico approach.

In cyanobacteria, carbonic anhydrase (zinc metalloenzyme) is a major enzyme that converts CO₂ to HCO₃- maintaining the carbon concentration around the vicinity of RuBisCo, leading to cyanobacterial biomass generation. Anthropogenic activities, disposal of leached micro nutrients effluents from industries into the aquatic environment results in cyanobacterial blooms. The harmful cyanobacteria release cyanotoxins in open-water system which on ingression through oral route causes major health issues like hepatotoxicity and immunotoxicity. A database was prepared consisting of approximately 3k phytochemicals curated from previous literatures, earlier identified by GC-MS analysis. The phytochemicals were subjected to online servers to identify the novel lead molecules which followed ADMET and drug-like candidates. The identified leads were optimized by density functional theory method using B3YLP/G* level of theory. Carbonic anhydrase chosen as target to observe the binding interaction through molecular docking simulations. From the molecules included in the database the highest binding energy exhibited by alpha-tocopherol succinate and mycophenolic acid were found to be -9.23 kcal/mol and -14.41 kcal/mol and displayed interactions with GLY A102, GLN B30, ASP A41, LYS A105 including Zn²⁺ and their adjacent amino acids CYS 101, HIS 98, CYS 39 in both chain A and chain A-B of carbonic anhydrase. The Identified molecular orbitals decipher computed global electrophilicity values (Energy gap, electrophilicity and Softness) of alpha-tocopherol succinate and mycophenolic acid were found to be (5.262, 1.948, 0.380) eV and (4.710, 2.805, 0.424) eV demonstrates both molecules are effective and stable. The identified leads may serve as a better anti-carbonic anhydrase agent because they accommodate in the binding site and hampers the catalytic activity of Carbonic anhydrase thus inhibiting the generation of cyanobacterial biomass. This identified lead molecules may serve as a substructure to design novel phytochemicals against carbonic anhydrase present in cyanobacteria. Further in vitro study is necessary to evaluate the efficacy of these molecules.