Semicarbazones, thiosemicarbazone, thiazole and oxazole analogues as monoamine oxidase inhibitors: Synthesis, characterization, biological evaluation, molecular docking, and kinetic studies

• Published in: Bioorganic chemistry 2021-10, Vol.115, p.105209-105209, Article 105209
• Main Authors: Qazi, Syeda Uroos, Naz, Asia, Hameed, Abdul, Osra, Faisal Abdulrhman, Jalil, Saquib, Iqbal, Jamshed, Shah, Syed Adnan Ali, Mirza, Agha Zeeshan
• Format: Article
• Language: English
• Subjects: Dose-Response Relationship, Drug; Humans; Kinetic studies; Kinetics; MAO inhibition; Molecular docking; Molecular Docking Simulation; Molecular Structure; Monoamine Oxidase - metabolism; Monoamine Oxidase Inhibitors - chemical synthesis; Monoamine Oxidase Inhibitors - chemistry; Monoamine Oxidase Inhibitors - pharmacology; Oxazoles; Oxazoles - chemistry; Oxazoles - pharmacology; Semicarbazide; Semicarbazones; Semicarbazones - chemistry; Semicarbazones - pharmacology; Structure-Activity Relationship; Thiazoles; Thiazoles - chemistry; Thiazoles - pharmacology; Thiosemicarbazones - chemistry; Thiosemicarbazones - pharmacology
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.105209

A series of semicarbazone, thiosemicarbazone, and pyrazole derivatives (3a-3m) were designed, synthesized, and assessed for monoamine oxidase inhibition using two isoforms. [Display omitted] •A series of hydrazine-carboxamide, hydrazine-carbothioamide, and pyrazole analogues were synthesized.•Examined for monoamine oxidase inhibition using two isoforms, MAO-A and MAO-B.•Molecular dockingandin-silicoADMEevaluation. A series of semicarbazone, thiosemicarbazone, thiazole, and oxazole derivatives were designed, synthesized, and examined for monoamine oxidase inhibition using two isoforms, i.e., MAO-A and MAO-B. Among all the analogues, 3c and 3j possessed substantial activity against MAO-A with IC50 values of 5.619 ± 1.04 µM and 0.5781 ± 0.1674 µM, respectively. Whereas 3d and 3j were active against monoamine oxidase B with the IC50 values of 9.952 ± 1.831 µM and 3.5 ± 0.7 µM, respectively. Other derivatives active against MAO-B were 3c and 3g with the IC50 values of 17.67 ± 5.6 µM and 37.18 ± 2.485 µM. Moreover, molecular docking studies were achieved for the most potent compound (3j) contrary to human MAO-A and MAO-B. Kinetic studies were also performed for the most potent analogue to evaluate its mode of interaction with MAO-A and MAO-B.