Microwave Facilitated Discovery of Substituted 1,2,4-triazaspiro[4.5] dec-2-en-3-amines: Biological and Computational Investigations

Abstract

Background: Tuberculosis is an effectual infectious disease caused by the spread of tu-bercular bacteria within the lungs via droplets of coughs and sneezes. In 2021, 1.6 million people died due totuberculosis, which is the 13th leading killer disease and 2nd leading after COVID-19 infectious disease. Objective: Many drugs are available as antitubercular drug, but still, requires more efficacious drug molecules with lower toxicity, side effects and small-sized molecules. To fulfill said prospective, computational study such as molecular docking and ADMET studies guides towards an ideal drug molecule with small -sized, unique spiro structures. Methods: Conventional and microwave-initiated Reaction of cyclohexanone, hydrazine carbothio-amide, and 2-amino-4-methoxy-6-methyl-1,3,5-triazine affords compound 1, which is subjected to the Schiff base reaction with diverse aldehydes. All structures are defined using IR, 1H NMR, 13C NMR, and mass spectroscopy. The entire series is exposed to in vitro antibacterial and antitubercu-lar and in silico molecular docking and ADMET studies. Results: Compounds 2c and 2b have been established to be potential antibacterial agents, whereas compounds 2d, 2e, 2j, 2k and 2l are extremely effective against tubercular strains. Furthermore, molecular docking of related molecules is performed, and compounds 2d, 2e, 2j, 2k, and 2l have higher affinities toward antitubercular proteins. ADMET parameters such as water solubility, SA score, PCaco2 value, and TPSA values are satisfactory. Conclusion: The microwave method has been proven to be a greener method as compared to the con-ventional heating method. Comparative results of in vitro analysis are obtained with referenced anti-bacterial drugs and antitubercular drugs. In silico observations supports their in vitro assessments. Appraisal obtained from the ADMET study leads to the formation of ideal drug molecules.