Macrocyclic peptidomimetics with antimicrobial activity: synthesis, bioassay, and molecular modeling studies

Abstract

Novel, cyclic peptidomimetics were synthesized by facile acylation reactions using benzotriazole chemistry. Microbiological testing of the synthesized compounds revealed an exceptionally high activity against Candida albicans with a minimum inhibitory concentration (MIC) two orders of magnitude lower than the MIC of the antifungal reference drug amphotericin B. A strikingly high activity was also observed against three Gram-negative bacterial strains (Pseudomonas aeruginosa, Klebsiella pneumoniae and Proteus vulgaris), two of which are known human pathogens. Thus the discovered chemotype is a potential polypharmacological agent. The toxicity against mammalian tumor cells was found to be low, as demonstrated in five different human cell lines (HeLa, cervical; PC-3, prostate; MCF-7, breast; HepG2, liver; and HCT-116, colon). The internal consistency of the experimental data was studied using 3D-pharmacophore and 2D-QSAR.

Synthesis, characterization and carbonic anhydrase inhibitory activity of novel benzothiazole derivatives

“…New N-protected amino acid benzothiazole conjugates (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) were synthesized by the treatment of appropriate benzothiazole derivatives and N-protected amino acid (Gly, Ala and Phe) derivatives under microwave heating at 70 C for 45 min with good yields of 60-70%. The compound 13 was synthesized from the reacting of (S)-tert-butyl (1-( (4- As it is seen in Table 1 none of the N-protected amino acidbenzothiazole conjugates 1-13 showed affinity toward to membrane-associated isoform hCA IV and compounds 12 and 13 are inactive on four hCAs tested in this study.…”

“…On the other hand, short peptides and their conjugates exhibit a broad spectrum of biological activity. Recently, one of our groups reported biological properties of some peptide 10 and their conjugates 11 . In the light of our prior studies, the current work expands the studies on synthesis of novel benzothiazole N-protected amino acid conjugates with the aim to combine two important scaffolds in one structure.…”

Green and catalyst-free synthesis of olsalazine analogs

“…We previously used benzotriazole methodology to prepare diverse peptide conjugates (13)(14)(15)(16)(17).…”

Synthesis and carbonic anhydrase I, II, IV and XII inhibitory properties of N-protected amino acid – sulfonamide conjugates

“…Melting points (mp) were measured in open capillary tubes and are uncorrected, using a Gallenkamp MPD350.BM3.5 apparatus. N-protected amino acids 19,[43][44][45] ; 47 were found in the literature but their synthesis methods need harsh reaction conditions and cumbersome work-up procedures. Thus, these compounds were synthesized by a new, one-step, easy synthetic method, using N-(protected a-aminoacyl)benzotriazoles in this work.…”