Mechanochemical synthesis of cyclohexenones and indazoles as potential antimicrobial agents

Mechanical force from ball milling was used for efficient and quantitative preparation of a series of cyclohexenones and indazoles. The method is environmentally friendly, simple, short, and solventless. Unambiguous structural assignments of the obtained cyclohexenones were achieved based on single-crystal X-ray diffraction. The structures of the indazoles were characterized using Fourier-transform infrared spectroscopy, hydrogen and carbon nuclear magnetic resonance (NMR) spectroscopy, homonuclear correlation spectroscopy, distortionless enhancement by polarization transfer (DEPT) NMR, and gas chromatography-mass spectrometry. The synthesized compounds were screened for antimicrobial activity against two Gram-positive bacteria (methicillin-resistant staphylococcus aureus and Micrococcus luteus), three Gram-negative bacteria (Klebsiella oxytoca, Salmonella typhimurium, and Shigella sonnei), and three fungi (Candida albicans, Aspergillus niger, and A. flavus). The effects that different substituents on the synthesized compounds had on the antibacterial and antifungal activities were evaluated. Cyclohexenone derivatives with thiophene moiety at 4-position showed antibacterial activity comparable to the antibiotic tetracycline. [GRAPHICS]