Three isomeric 4-[(n-bromophenyl)carbamoyl]butanoic acids (n = 2, 3 and 4) as DNA intercalator: Synthesis, physicochemical characterization, antimicrobial activity, antioxidant potential and in silico study

• Published in: Journal of molecular structure 2022-08, Vol.1262, p.133033, Article 133033
• Main Authors: Hanifa, Bibi, Sirajuddin, Muhammad, Kubicki, Maciej, Tiekink, Edward R.T.
• Format: Article
• Language: English
• Subjects: 4-[(n-bromophenyl) carbamoyl]butanoic acids; Antimicrobial activity; DNA intercalator; DPPH scavenging; In silico study; X-ray crystallography
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.133033

•Synthesis of three isomeric 4-[(n-bromophenyl)carbamoyl]butanoic acids.•Structural and spectroscopic characterization.•Interaction with SSDNA via intercalative mode of interaction.•Antioxidant and antimicrobial activities.•In silico study. A series of three isomeric 4-[(n-bromophenyl)carbamoyl]butanoic acids (n = 2, 3 and 4) were synthesized and their structures were confirmed by FTIR, NMR, MS, micro elemental analysis (CHN) and single crystal X-ray crystallography. Kinks are noted in the molecular structures of the n = 2 and n = 3 compounds, namely about the methylene-C–C(carbonyl) and N–C(phenyl) bonds; no such twist about the former bond is seen in the n = 4 molecule. In the molecular packing, supramolecular tapes are evident, being constructed by orthogonally orientated O-H…O(carbonyl) and N-H…O(amide) hydrogen bonds. The synthesized compounds interact with salmon sperm DNA via an intercalative mode as confirmed by the UV-visible spectroscopic and viscometric techniques. The results of antimicrobial activity performed against five bacterial and two fungal strains show that these compounds have < 50% inhibition. Compound 3 has shown the maximum of 78% DPPH scavenging activity. SwissADME webserver was used for in silico study of the screened compounds and it was found that they obey the rules of drug-likeness and exhibit good potential for bioavailability. Synopsis graphical abstract: the three isomeric carboxylic acid derivatives interact with SS-DNA via intercalative mode which was confirmed by UV/Vis. Spectroscopy and viscometery. They have shown moderate antimicrobial and good antioxidant potenmitals. [Display omitted]