Synthesis, Cytotoxicity and Antioxidant Activity of New Analogs of RC-121 Synthetic Derivatives of Somatostatin

Title:Synthesis, Cytotoxicity and Antioxidant Activity of New Analogs of RC-121 Synthetic Derivatives of Somatostatin

Volume: 18 Issue: 10

Author(s): Emilia Naydenova, Diana Wesselinova*, Svetlana Staykova, Ivan Goshev and Ljubomir Vezenkov

Affiliation:

• Institute of General and Comparative Pathology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Bl. 25, 1113 Sofia,Bulgaria

Keywords: Antioxidant, cytotoxic, somatostatin analogs, SPPS, unnatural amino acids, RC-121 synthetic.

Abstract: 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.

Cite this article as:

Naydenova Emilia, Wesselinova Diana*, Staykova Svetlana , Goshev Ivan and Vezenkov Ljubomir, Synthesis, Cytotoxicity and Antioxidant Activity of New Analogs of RC-121 Synthetic Derivatives of Somatostatin, Anti-Cancer Agents in Medicinal Chemistry 2018; 18 (10) . https://dx.doi.org/10.2174/1871520618666180417164344