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


Yilmaz Z. T., Odabasoglu H. Y., Senel P., Yuzbasioglu E. C., ERDOĞAN T., Ozdemir A., ...More

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Publication Date: 2022
  • Doi Number: 10.1080/07391102.2022.2061595
  • Journal Name: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Keywords: Phthalide, 2-aminothiazole, DNA binding, quorum sensing, antibacterial, molecular docking, ABSOLUTE ELECTRONEGATIVITY, SYNTHETIC METHODOLOGIES, ANTIBACTERIAL ACTIVITY, BIOLOGICAL EVALUATION, ANGELICA-SINENSIS, PHTHALIDES, 2-AMINOTHIAZOLES, BACTERIA, HARDNESS, CONFORMATION
  • Istanbul Technical University Affiliated: Yes

Abstract

A new 3-(5-methyl-2-thiazolylamino)phthalide molecule, 3-((5-methylthiazol-2-yl)amino)isobenzofuran-1(3H)-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(1/c) with unit-cell parameters a = 8.0550(6) angstrom, b = 6.1386(3) angstrom, c = 23.3228(18) angstrom, beta = 97.724(6)degrees and Z = 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 Chromobacterium violaceum 12472 and additionally for its antibacterial activity against Staphylococcus aureus 29213, Staphylococcus epidermidis 12228, Pseudomonas aeruginosa 27853, Escherichia coli 25922, and Proteus mirabilis 14153. The lowest MIC value was 0.24 mu g/mL for S. aureus 29213 and the highest MIC value was 30.75 mu g/mL for E. coli 25922. While anti-bacterial activity was observed in those other than the S. epidermidis and P. Mirabilis, anti-QS activity wasn't detected. Investigations on dsDNA binding affinity indicate that the title compound binds to dsDNA via 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