Isoleucine with secondary sulfonamide functionality as anticancer, antibacterial and antifungal agents

Abstract

Isoleucine substituted analogues with secondary sulfonamide group (I₁–I₆) have been synthesized. Structures of synthesized analogues have been confirmed by Fourier Transform-Infrared Red, Nuclear Magnetic Resonance (¹H and ¹³C) and ESI-MS spectroscopic tools. Cytotoxic screenings of synthesized analogues have been done on MCF-7 (breast), Prostate Cancer-3 (PC-3) and A549 (lung) cancer cell lines. N-(1-isobutyl-2-oxo-2-anilinoethyl) p-toluene sulfonamide (I₅) screened to be better cytotoxic agent on MCF-7 and A549 cell lines whereas N-(1-isobutyl-2-oxo-2-p-chloroanilino ethyl) benzene sulfonamide (I₃) against PC-3 cell line. Cell cycle analysis of N-(1-isobutyl-2-oxo-2-anilinoethyl) p-toluene sulfonamide (I₅) analogue has been carried out on A549 cell line in comparison to control and Vinblastine (standard drug). Complete arrest in G0 and G1 phase along with mild disturbance in S-phase of cell cycle has been observed. The screened analogues (I₁–I₆) also showed good antifungal and antibacterial potential against gram positive as well as gram negative strains. Computer simulation indicated good bioactivity prediction by the ‘Lipinski rule’ and synthesized analogues did not violate this rule. Docking study of isoleucine sulfonamide analogues (I₁–I₆) were carried out to determine the possible interaction sites of the analogues with p53 tumor suppressor-DNA complex and demonstrate that the analogues confirmed binding and inhibition with the most mutated residues of p53. Density functional theory has been used to correlate the electronic and chemical properties of analogues and they were found to be stable and chemically reactive. Thus the results suggest that isoleucine substituted sulfonamide analogues can serve as a structural model for the design of anticancer agents, antibacterial agents as well as antifungal agents with better inhibitory potential.

Communicated by Ramaswamy H. Sarma

Keywords:

• Antibacterial and antifungal
• bioactivity
• cytotoxicity
• density functional theory
• FT-IR
• isoleucine amino acid
• Lipinski rule
• molecular docking
• sulfonamide

Acknowledgements

Thanks to SAIF lab, PU Chandigarh for ¹H-NMR, ¹³C-NMR, ESI-MS, and FT-IR spectroscopic experiments. Authors thank Anti-Cancer Drug screening facility (ACDSF) at ACTREC, Tata Memorial Centre, Navi Mumbai for cytotoxic study. Thanks to Pharmacology and Toxicology lab (CSIR-IHBT), Palampur, Himachal Pradesh for cell-cycle analysis. We are thankful to Dr. Sunita Siwach, Ubiquitous Analytical Techniques Lab, CSIR-CSIO Chandigarh for antibacterial and antifungal studies. This research work is also filed as Indian patent with Application no. 202011017638. We are thankful the Director, National Institute of Technology, Hamirpur (H.P) India for extending all laboratory and administrative facilities.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work is financially supported by UGC-RGNF, New Delhi, India (F1-17.1/2014-15/RGNF-2014-15-ST-HIM-84222/(SAIII/website)).