Design, Synthesis and In vitro Antitubercular Effect of New Chalcone Derivatives Coupled with 1,2,3‐Triazoles: A Computational Docking Techniques

Abstract A very interesting foundation for this study is the creation of new methods for modifying compounds with a 1,2,3‐triazole and chalcone scaffolds, as these compounds are significant in organic synthesis, particularly in the synthesis of bioactive organic compounds. To contribute to the development of an efficient method for the conversion of antimicrobial and antituberculosis heterocyclics, a novel series of cyclohepta pyridinone fused 1,2,3‐triazolyl chalcones were designed and synthesized. All the newly prepared scaffolds were characterized by FT‐IR, NMR ( 1 H & 13 C) and mass spectrometry. Among the tested compounds, hybrids 8b , 8d , and 8f exhibited exceptional antibacterial susceptibilities with zone of inhibition 27.84±0.04, 32.27±0.02, and 38.26±0.01 mm against the tested E. faecalis bacteria, whereas 8d had better antitubercular potency against M. tuberculosis H 37 Rv strain with MIC value 5.25 μg/mL, compared to Streptomycin [MIC=5.01 μg/mL]. All the synthesized compounds were initially assessed in silico against the targeted protein i. e., DprE1 that indicated compound 8d, 8f and 8h along with several other 1,2,3‐triazole compounds as possible inhibitors. Based on docking results, 8d showed that the amino acids His 74 (A), Lys 76 (A), Cys 332 (A), Asp 331 (A), Val 307 (A), Tyr 357 (A), Met 226 (A), Gln 276 (A), Gly 75 (A), Peo 58 (A), Leu 259 (A), and Lys 309 (A) exhibited highly stable binding to DprE1 receptor of Mycobacterium tuberculosis (PDB: 4G3 U). Moreover, these scaffolds physicochemical characteristics, filtration molecular properties, assessment of toxicity, and bioactivity scores were assessed in relation to ADME (absorption, distribution, metabolism, and excretion).