Curcumin-Based Heterocycles: Synthesis, Antimicrobial Genotoxicity and Molecular Docking

Abstract

Curcumin is a natural compound with numerous biological activities and a precursor for many drugs. Development of a convenient one pot synthetic method for synthesizing curcumin-based diazepines and diazoles having antibacterial activities is focussed in this study. A one pot condensation process was developed for synthesizing a novel class of curcumin-based diazoles and diazepines by reacting curcumin with 2-diamino compounds and hydrazines in presence of sulfuric acid as catalyst. IR and 1H NMR were used to characterize the molecular composition of the synthesized curcumin derivatives. The synthesized derivatives were tested for their in vitro antibacterial efficacy against Gram-negative and Gram-positive bacteria. The MIC concentrations ranged from 1.56 to 200 μg/mL. Ampicillin exhibited synergistic effects with compounds C1, C3, C4 and C8. In the genotoxicity test, compound C3 was found to have no effect on the DNA molecules of E. coli strains, suggesting that it is not mutagenic and/or genotoxic. Compound C2 had the strongest interaction with the investigated protein receptor sites when blind molecular docking was conducted on all compounds. Since both H-donating and H-accepting sites of this molecule interact efficiently during the docking. In addition, absorption, distribution, metabolism and excretion (ADME) study showed that compound C2 do not contradict the Lipinski’s rule of drug likeness and showed a low level of passive human gastrointestinal absorption. The results indicated that C2 could be most promising among the studied compounds.