New triazinyl-benzenesulfonamide conjugates with amino acids: Design, synthesis and biological activity

Derivatives of 1,3,5‐triazine have been extensively studied for their broad range of biological properties. Increased interest in the 1,3,5-triazine core has led to the synthesis of many compounds with promising biological activities. Various triazine derivatives are often studied as a part of several therapeutic agents, e.g. antibacterial, antifungal, antimalarial, anticarcinogenic, antiviral, and anticonvulsant agents [1-2]. Very important are 1,3,5-triazinyl-aminobenzenesulfonamide derivatives which are designed, for example, to inhibit human carbonic anhydrases [3]. Their antimicrobial activity against E. coli, P. aeruginosa, C. albicans, S. aureus as well as their effect on cancer cell proliferation is also being investigated [4-5].

In this context, a series of benzenesulfonamide derivatives with 1,3,5-triazine, incorporating various amino acids were prepared. The compounds were isolated and purified by semi-preparative LC methods and their molecular structures were confirmed by ¹H, ¹³C NMR, IR spectroscopy and HPLC-DAD/MS analysis. Antioxidant activity of compounds was screened by DPPH, ABTS, and FRAP assay. The antimicrobial activity against C. albicans, E. coli, methicillin-resistant S. aureus, M. smegmatis, E. faecalis, as well as E. faecium was monitored. As there are several derivatives with a 1,3,5-triazine ring and amino acid residues in the structures of several anticancer agents, the MTT assay was used to evaluate the anticancer activity. Primary screening of the antitumor activity of selected new derivatives with amino acids with non-polar (Ala, Trp, Ile) side chains and their precursors was performed against the human colorectal adenocarcinoma cancer cell line HT-29 in order to select promising derivatives. Data obtained in this study could be useful for further study and evaluation of this class of compounds. The cytotoxic effect of 1,3,5-triazinyl-benzenesulfonamide conjugates with amino acids will be further discussed in our contribution.