Synthesis of some benzimidazole deriatives bearing amino acid groups

Benzimidazole derivatives are interesting heterocycles because they are present in many naturally occurring products and various drugs. They also an important pharmacophore in modern drug discovery and continue to be the most versatile class of compounds possessing different pharmacological activities such as antitumor, diuretic, fungicidal, bactericidal, antihelmintic, antiallergic, antihistaminic, vasodilator, hipotensive, spasmoliytic activities and local analgesic. Moreover, benzimidazoles is of a considerable interest as a ligand toward transition metal ions with a variety of biological molecules including ionheme systems, vitamin B12 and its derivatives, and several metalloproteins. For this reason, the complexes of transition metal salts with benzimidazole derivatives have been extensively investigated as model structure of some important biological molecules. On the other hand, it is known that short peptide sequences present a broad spectrum of biological activity. Peptide-protein interactions are central to cell biology. It is also known that, low molecular weight peptides can easily cross biological barriers, are less susceptible to protease attacks. The synthesis of peptides and proteins is of great importance to the understanding of biological functions. Although peptides and proteins mediate numerous biological process, their use as therapeutic agents is often accompanied by several drawbacks, including poor bioavailability, low biostability, and limited receptor subtype selectivity. Therefore, much effort has been expended on the design and synthesis of selective, high-affinity ligands by replacing portions of peptides with nonpeptide structures. The benzimidazole rings with heteroaromatic structure have excellent stabilities derived from its molecular symmetry and aromaticity, so the incorporation of benzimidazole group into peptide backbone would bear without deterioration of their own excellent properties. In this respect, the synthesis of biological important active molecules which are similar to the biological systems from the reacting various peptides with benzimidazole or benzimidazole derivatives are especially important. There is extremely limited information in the literature on this subject. Within the framework of this project, a series of new benzimidazole containing amino acids and peptides (1-20) as given at below scheme were synthesized and their structures were identified by 1H NMR, 13C NMR, IR and elemental analysis. . Some of the synthesized derivatives were screened for their in vtro antimicrobial activities against standard strains; Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 29213, Pseudomonas aureus ATCC 27853 ve Enterococcus faecium NJ-1 and the yeasts Candida albicans and Candida tropicalis.