Polycystic Ovary Syndrome (PCOS) Inhibitory Drug Screening from Selective Inositols

Abstract

Sheikh Shohag, Shomaya Akhter, Saraban Tahura Antora, Kazi Ajija Nawer and Md. Abdul Alim

Polycystic ovary syndrome (PCOS) is a heterogeneous ailment characterized by a combination of symptoms, including signs of androgen excess (hirsutism and/or hyperandrogenemia), ovarian dysfunction-oligo-ovulation and/or polycystic ovarian morphology (PCOM)), reproductive abnormalities, obesity, menstrual irregularity, type 2 diabetes (T2DM), hypertension, dyslipidemia, and depression. PubChem, enriched with 110 million chemicals, yielded 6327 inositol derivatives. Lipinski rule of five (MW up to 500 g/mol, H-bond donors 1–5, H-bond acceptors up to 10) criteria has been used for filtration of 582 compounds initial stage. Using escalating molecular weight, 101 molecules were selected from 582, to control this and rogen. To explore the possibility of androgen inhibition, various computational approaches, such as PASSprediction,protein-ligand interactions through molecular docking, chemical descriptors by DFT study, ADMET, bioavailability, and molecular dynamic (MD) simulation, were adopted by using the most accepted methods. Out of 101 inositol derivatives, 90 compounds were found to have more testosterone-inhibiting properties than ovulation-inhibiting or insulin-promoting properties in the PASS prediction investigation. Molecular docking analysis reveals a binding propensity for inositols of more than -7.4 kcal/mol between the androgen receptor protein (3RLJ) and inositols. Some of the most frequent bonded sites are shown to be at the MET:745 and ARG:752 amino acid residues, where the ligand (inositols) forms both hydrogen and hydrophobic bonds. In contrast, the Density Functional Theory (DFT) was used to predict the chemical and physical characteristics of promising inositols in this research. Furthermore, ADME, toxicity, and carcinogenicity factors were analyzed to validate the drugs' potential as safe, effective treatments for PCOS.MD simulation was done for the ligands L60, L77, and L88 against the target protein. The result of RMSD and RMSF revealed that the stability of docked complex is very high. As a conclusion, the in silico research suggests that the three inositols (L60, L77, and L88) are the most promising candidates for PCOS-preventative drugs that still need clinical or additional study.

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