Conformation Study and Design of Novel 6-Hydroxybenzothiazole-2-Carboxamides as Potentially Potent and Selective Monoamine Oxidase B Inhibitors for Neuroprotection.

Background: 6-hydroxybenzothiazole-2-carboxamide is a novel, potent, and specific monoamine oxidase B inhibitor that can be used to study the structure of molecules and come up with new ways to protect neurons.

Objective: The objective of this work was to create an effective model using derivatives of 6- hydroxybenzothiazole-2-carboxamide and establish a dependable predictive foundation for the development of neuroprotective monoamine oxidase B inhibitors for the treatment of neurodegenerative diseases.

Methods: The construction and optimization of all compounds were carried out sequentially using ChemDraw software and Sybyl-X software. The optimized compounds were further analyzed using the COMSIA approach and the Sybyl-X software tool for QSAR modeling. A set of novel compounds of 6-hydroxybenzothiazole-2-carboxamide were created and their IC50 values were forecasted using QSAR modeling. Ultimately, the recently developed compounds underwent a screening process using their IC50 values, and molecular docking tests were conducted on the ten most promising compounds with the highest IC50 values.

Results: The 3D-QSAR model exhibited favorable outcomes. The value of q2 in the COMSIA model was 0.569. The model demonstrated a superior r2 value of 0.915, a lower SEE of 0.109, and a higher F-value of 52.714. The statistical findings and validation of the model were deemed adequate. Furthermore, analyzing the contour plots might assist in identifying the necessary structural specifications.

Conclusion: This work has the potential to provide an insight into the development of active medicines that protect the nervous system against neurodegenerative disorders.