Synthesis and Bioactivity of a Cyclopolypeptide from Caribbean Marine Sponge

Rajiv Dahiya; Stacy Rampersad; Terry G Ramnanansingh; Komalpreet Kaur; Ramninder Kaur; Rita Mourya; Suresh V Chennupati; Richard Fairman; Nigel K Jalsa; Ajay Sharma; Shivkanya Fuloria; Neeraj Kumar Fuloria

doi:10.22037/ijpr.2020.15405.13075

Synthesis and Bioactivity of a Cyclopolypeptide from Caribbean Marine Sponge

Iran J Pharm Res. 2020 Summer;19(3):156-170. doi: 10.22037/ijpr.2020.15405.13075.

Authors

Affiliations

¹ Laboratory of Peptide Research and Development, School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago.
² Department of Pharmaceutical Chemistry, GHG Khalsa College of Pharmacy, Gurusar Sadhar, Ludhiana, Punjab, India.
³ School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia.
⁴ Department of Pharmacy, College of Medical and Health Sciences, Wollega University, Nekemte, Ethiopia.
⁵ Department of Chemistry, Faculty of Science and Technology, The University of the West Indies, St. Augustine, Trinidad and Tobago.
⁶ Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, India.
⁷ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, AIMST University, Semeling, Bedong, Kedah, Malaysia.

Abstract

Synthesis of a natural proline-rich cyclopolypeptide - rolloamide A was carried out by coupling of tri- and tetrapeptide units Boc-Phe-Pro-Val-OMe and Boc-Pro-Leu-Pro-Ile-OMe after proper deprotection at carboxyl and amino terminals using carbodiimide chemistry in alkaline environment followed by cyclization of linear heptapeptide segment in the presence of base. The structure of synthesized peptide was confirmed by spectral techniques including FTIR, ¹H NMR, ¹³C NMR, MS analyses. Newly synthesized peptide was subjected to biological screening against pathogenic microbes and earthworms. Cyclopeptide 8 possessed promising activity against pathogenic fungi Candida albicans (ZOI: 24 mm, MIC: 6 μg/mL) and Gram-negative bacteria Pseudomonas aeruginosa (ZOI: 27 mm, MIC: 6 μg/mL) and Klebsiella pneumoniae (ZOI: 23 mm, MIC: 12.5 μg/mL), in comparison to reference drugs - griseofulvin (ZOI: 20 mm, MIC: 6 μg/mL) and ciprofloxacin (ZOI: 25 mm, MIC: 6 μg/mL/ZOI: 20 mm, MIC: 12.5 μg/mL). Also, newly synthesized heptacyclopeptide exhibited potent anthelmintic activity against earthworms Megascoplex konkanensis, Pontoscotex corethruses, and Eudrilus species (MPT/MDT ratio - 8.22-16.02/10.06-17.59 min), in comparison to standard drugs - mebendazole (MPT/MDT ratio - 10.52-18.02/12.57-19.49 min) and piperazine citrate (MPT/MDT ratio - 12.38-19.17/13.44-22.17 min).

Keywords: Anthelmintic activity; Antibacterial activity; Antifungal activity; Cyclic heptapeptide; Cyclization; Rolloamide A; Solution-phase peptide synthesis.