Synthesis molecular docking and DFT studies on novel indazole derivatives

Area of Science:

• Organic Chemistry
• Medicinal Chemistry
• Computational Chemistry

Background:

• The amide bond is a crucial functional group in diverse scientific domains.
• Indazole derivatives are of interest for their potential applications.

Purpose of the Study:

• To synthesize and characterize novel indazole derivatives via amide cross-coupling.
• To computationally evaluate the electronic properties and protein binding affinities of these derivatives.

Main Methods:

• Amide cross-coupling reactions for synthesis.
• Spectroscopic techniques (IR, 1H NMR, 13C NMR, Mass Spectrometry) for analysis.
• Density Functional Theory (DFT) for computational study.
• Molecular docking using Autodock 4 to assess protein interactions.

Main Results:

• Twenty-six indazole derivatives (8a-8z) were successfully synthesized.
• DFT analysis indicated compounds 8a, 8c, and 8s possess the largest HOMO-LUMO energy gap.
• Molecular docking revealed derivatives 8v, 8w, and 8y exhibited the highest binding energies with the renal cancer-related protein (PDB: 6FEW).

Conclusions:

• The synthesized indazole derivatives show promise for further investigation.
• Compounds 8a, 8c, and 8s are computationally stable.
• Derivatives 8v, 8w, and 8y demonstrate potential as inhibitors for the targeted renal cancer protein.