Molecular interaction of novel benzothiazolyl triazolium analogues with calf thymus DNA and HSA-their biological investigation as potent antimicrobial agents

• Published in: European journal of medicinal chemistry 2018-04, Vol.150, p.228-247
• Main Authors: Maddili, Swetha K., Katla, Ramesh, Kannekanti, Vijaya Kumar, Bejjanki, Naveen Kumar, Tuniki, Balaraju, Zhou, Cheng-He, Gandham, Himabindu
• Format: Article
• Language: English
• Subjects: Antibacterial; Calf thymus DNA; Human serum albumin; Imidazo [2,1-b] benzothiazole; Molecular docking; Triazole
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2018.02.056

The binding behaviour between calf thymus DNA and synthesized benzothiazolyl triazolium derivatives as potent antimicrobial agents was explored by means of spectroscopic applications together with molecular docking study at the sub-domain IIA, binding site I of human serum albumin (HSA). Most of the synthesized derivatives presented significant antimicrobial inhibition when compared with the clinical Norfloxacin, Chloromycin, and Fluconazole. In particular, compound 5q presented efficient anti-Bacillus subtilis, anti-Escherichia coli, anti-Salmonella typhi, and anti-Psuedomonas aeruginosa activity with low MIC values of 2–8 μg/mL which were relatively superior to the reference drugs. The preliminarily investigation of interaction studies with calf thymus DNA demonstrated that the most active compound 5q could effectively intercalate into DNA to form 5q-DNA complex. Further investigations revealed that human serum albumin could effectively transport compound 5q while molecular modelling studies with good docking score showed that hydrophobic interactions as well as hydrogen bonds played a significant role in the interaction of compound 5q with HSA. In addition, the cytotoxic investigation carried out on four different cancerous cell lines (3 human cell lines and 1 murine cell lines) by MTT assay presented that compound 5n is active against MDA cell lines with IC50 values less than 100 μg/mL. [Display omitted] •Novel imidazo [2,1-b] benzothiazolyl triazolium analogues were synthesized and assessed for antimicrobial activity.•Interaction mode between calf thymus DNA and compound 5q was explored by spectroscopic techniques.•Good molecular docking score revealed the interaction of compound 5q with HSA at sub-domain IIA binding site.•Cytotoxic investigation was carried out on four different cancerous cell lines by MTT Assay.