Identification of a 3-(5-methyl-2-thiazolylamino)phthalide as a new minor groove agent.

A new 3-(5-methyl-2-thiazolylamino)phthalide molecule, 3-((5-methylthiazol-2-yl)amino)isobenzofuran-1(3)-one, was synthesized and characterized experimentally by FT-IR, NMR, UV-Vis, and single-crystal X-ray analysis and theoretically by quantum chemical calculations. The single-crystal X-ray studies revealed that the compound crystallizes in the monoclinic space group P-2 with unit-cell parameters  = 8.0550(6) Å,  = 6.1386(3) Å,  = 23.3228(18) Å,  = 97.724(6)° and  = 4. Optimized geometries and the vibrational frequencies were studied at the density functional theory (DFT) level by using the hybrid functional B3LYP with a 6-311 G (d,p) basis set. The title compound was evaluated for its anti-quorum sensing (anti-QS) activity on 12472 and additionally for its antibacterial activity against 29213, 12228, 27853, 25922, and 14153. The lowest MIC value was 0.24 μg/mL for 29213 and the highest MIC value was 30.75 μg/mL for 25922. While anti-bacterial activity was observed in those other than the and , anti-QS activity wasn't detected. Investigations on dsDNA binding affinity indicate that the title compound binds to dsDNA the groove binding mode. Molecular docking calculations and molecular dynamics simulations results showed also that the title compound prefers binding to the minor groove of dsDNA and remains stable in the minor groove throughout the molecular dynamics simulation.Communicated by Ramaswamy H. Sarma.