Background:
Based on the structure of RC-121 (D-Phe-c (Cys-Tyr-D-Trp-Lys-Val-Cys)-Thr-NH2, -
synthetic derivatives of somatostatin), some analogs were synthesized and tested for in vitro cytotoxic and antioxidant
activity.
Objectives:
The new analogs were modifyed at position 5 with Dap (diaminopropanoic acid), Dab (diaminobutanoic
acid) and Orn and at position 6 with the unnatural amino acids Tle (t-leucine).
Methods:
The in vitro cytotoxic effects of the substances were investigated against a panel of human tumor cell
lines HT-29 (Human Colorectal Cancer Cell Line), MDA-MB-23 (Human Breast Cancer Cell Line), Hep G-2
(Human Hepatocellular Carcinoma Cell Line) and HeLa (cervical cancer cell line). The antioxidant capacities
were tested by ORAC (Oxygen Radical Antioxidant Capacity) and HORAC (Hydroxyl Radical Averting Capacity)
methods.
Results:
All substances expressed significantly higher antioxidant capacity by comparison with galic acid and
Trolox. All substances showed considerable antioxidant capacity as well. Compound 2T (D-Phe-c(Cys-Tyr-DTrp-
Dap-Tle-Cys)-Thr-NH2)had the highest antioxidant effect. The compound 4T (D-Phe-c(Cys-Tyr-D-Trp-
Orn-Tle-Cys)-Thr-NH2) displayed antiproliferative effect on HeLa cells with IC50 30 µM. The peptide analog 3T
(D-Phe-c(Cys-Tyr-D-Trp-Lys-Tle-Cys)-Thr-NH2) exerted the most pronounced inhibition on the cell vitality up
to 53%, 56% and 65% resp. against MDA-MB-23, Hep G-2, HeLa in the higher tested concentration.
Conclusion:
The somatostatin analogs showed moderate influence on the vitality of different tumor cells and
could be used in changing their pathology.
Synthesis of bis-Heterocyclic Derivatives of Thiohydantoin
