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

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.

Sulfonamide phenylalanine (SPA) series of analogues as an antibacterial, antifungal, anticancer agents along with p53 tumor suppressor-DNA complex inhibitor - part 1.

A series of N-[1-benzyl-2-oxo-2-substituted(ethyl)] benzene/p-toluene sulfonamide (K1-K12) are synthesized. Structure of the synthesized analogues has been confirmed by FT-IR, 1H & 13C NMR and ESI-MS spectroscopic techniques. All the synthesized analogues (K1-K12) have also been examined for their in-vitro antibacterial and antifungal activities. Compounds showed good antibacterial and antifungal activity against standard drug. Anticancer study has been carried out on three cancer cell lines PC-3, MCF-7 and A549 on two different concentrations (mg/mL and µg/mL). The K4 sulfonamide analogue showed better anticancer activity amongst all analogues against PC-3 and A549 cell lines. K4 inhibit G0/G1 phase in cell-cycle analysis experiment. All synthesized molecules (K1-K12) dock at junction p53-DNA and make hydrogen bonded with residues of p53 protein as per docking study. ADMET predictions of synthesized phenylalanine sulfonamide analogues (K1-K12) has been done using 'Lipinski rule' and it has been observed that all synthesized analogues did not violate the rule. Electronic, chemical properties and mulliken atomic charges of analogues were calculated using density functional theory (DFT). Communicated by Ramaswamy H. Sarma.