SYNTHESIS OF KNOEVENAGEL DERIVATIVES AND THEIR MOLECULAR DOCKING STUDIES FOR BLOOD CANCER

Abstract

Knoevenagel condensation, a carbon-carbon bonding process, produces bioactive chemicals. Knoevenagel derivatives made with aromatic aldehydes may treat leukemia and lymphoma. The structural and electronic properties of aromatic aldehydes and active methylene reagents enabled the creation of various α, β-unsaturated carbonyl compounds. Mass, IR, and 1H-NMR confirmed the changed derivatives' structure. Lab tests examined their antibacterial and antifungal properties. Six novel knoevenagel derivatives (1a 6a) were computationally evaluated and synthesised as potential SOD3 inhibitors for hematological malignancies. After rigorous molecular docking simulations (AutoDock Vina, exhaustiveness=16), compound 2a was the most potent candidate with a binding affinity of -4.953 kcal/mol and an optimal combination of hydrogen bonds with catalytic residues (ASP500, ASN487) and extensive hydrophobic interactions (LEU489, ILE369). Structure-activity analysis identified three key inhibitor factors: (1) hydrogen bonding with catalytic residues, (2) hydrophobic complementarity with ALA389 Despite multiple hydrogen bonds, compound 5a performed poorly (-1.975 kcal/mol), emphasizing steric compatibility. Computational predictions indicate active site competition, allosteric modulation, and cysteine coordination-mediated redox interference. Our findings support the development of next-generation knoevenagel-based SOD3 inhibitors, with compound 2a promising for blood cancer treatment.