Design of potential reverse transcriptase inhibitor containing Isatin nucleus using molecular modeling studies

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Drug Discovery

Background:

• HIV remains a global health challenge, necessitating novel therapeutic agents.
• Isatin analogues have shown potential antiviral properties.
• Quantitative Structure-Activity Relationship (QSAR) studies are crucial for rational drug design.

Purpose of the Study:

• To design and synthesize novel Isatin analogues with enhanced anti-HIV activity.
• To establish correlations between chemical structure and anti-HIV activity using QSAR.
• To evaluate the binding affinity and ADME properties of designed compounds.

Main Methods:

• Two-Dimensional (2D) and Three-Dimensional (3D) QSAR studies employing Multiple Linear Regression (MLR) and k Nearest Neighbor Molecular Field Analysis (kNN MFA).
• Molecular docking studies to assess binding affinity to the Reverse Transcriptase enzyme.
• Synthesis of novel Isatin analogues and experimental evaluation using Reverse Transcriptase Assay.
• Prediction of Absorption, Distribution, Metabolism, and Excretion (ADME) properties.

Main Results:

• QSAR models successfully correlated chemical structure with anti-HIV activity.
• Designed New Chemical Entities (NCEs) showed promising binding affinities.
• Three synthesized Isatin analogues exhibited significant Reverse Transcriptase inhibition, outperforming the standard drug Navirapine.
• Structure-Activity Relationships (SAR) were elucidated based on computational and experimental findings.

Conclusions:

• The study successfully identified potent Isatin-based anti-HIV agents through integrated computational and experimental approaches.
• The developed QSAR models provide a valuable framework for designing future anti-HIV compounds.
• The synthesized compounds represent promising leads for further development into anti-HIV therapeutics.