Prva potpuna sinteza i biološko vrednovanje himenamida E

A new potent bioactive, proline-rich cyclic heptapeptide hymenamide E (13) was synthesized using the solution phase technique by cyclization of the linear peptide Boc-Phe-Pro-Thr-Thr-Pro-Tyr-Phe-OMe (12) after proper deprotection at carboxyl and amino terminals. Linear peptide segment was prepared by coupling the tripeptide unit Boc-Phe-Pro-Thr-OH (10a) with the tetrapeptide unit Thr-Pro-Tyr-Phe-OMe (11a) using dicyclohexylcarbodiimide as the coupling agent and N-methylmorpholine as the base. Structures of all new compounds were characterized by IR, 1H NMR spectral data as well as elemental analyses. In addition, the structure of compound 13 was verified by 13C NMR, fast atom bombardment mass spectroscopy and differential scanning calorimetry. The newly synthesized cyclopeptide was screened for its antibacterial, antifungal and anthelmintic activities against eight pathogenic microbes and two earthworm species. Compound 13 showed potent antifungal activity against Candida albicans and Ganoderma species comparable to that of griseofulvin as a reference drug and potent anthelmintic activity against earthworms Megascoplex konkanensis and Eudrilus species in comparison to piperazine citrate.Novi biološki aktivni ciklički heptapeptid himenamid E (13) sintetiziran je ciklizacijom linearnog peptida Boc-Phe-Pro-Thr-Thr-Pro-Tyr-Phe-OMe (12) nakon uklanjanja zaštitnih skupina sa C-terminalnih i N-terminalnih aminokiselina. Linearni peptidni segment pripravljen je spajanjem tripeptidne jedinice Boc-Phe-Pro-Thr-OH (10a) s tetrapeptidnom jedinicom Thr-Pro-Tyr-Phe-OMe (11a) u prisutnosti dicikloheksilkarbodiimida i N-metilmorfolina kao baze. Strukture novih spojeva potvrđene su IR i 1H NMR spektroskopijom i elementarnom analizom, a struktura spoja 13 i 13C NMR, spektroskopijom masa i diferencijalnom pretražnom kalorimetrijom. Novosintetizirani ciklopeptid testiran je na antibakterijsko, antifungalno i anthelmintičko djelovanje na osam patogenih mikroorganizama i dva parazita. Spoj 13 snažno djeluje antifungalno na gljivice Candida albicans i vrste Ganoderma i anthelmintički na nametnike Megascoplex konkanensis i vrste Eudrilus. Kao poredbene ljekovite tvari uporabljeni su grizeofulvin i piperazin citrat