First Total Synthesis and Pharmacological Potential of a Plant Based Hexacyclopeptide

Rajiv Dahiya; Sunil Singh; Sheeba Varghese Gupta; Vijaykumar B Sutariya; Deepak Bhatia; Rita Mourya; Suresh V Chennupati; Ajay Sharma

doi:10.22037/ijpr.2019.1100643

First Total Synthesis and Pharmacological Potential of a Plant Based Hexacyclopeptide

Iran J Pharm Res. 2019 Spring;18(2):938-947. doi: 10.22037/ijpr.2019.1100643.

Authors

Rajiv Dahiya¹, Sunil Singh², Sheeba Varghese Gupta³, Vijaykumar B Sutariya³, Deepak Bhatia⁴, Rita Mourya⁵, Suresh V Chennupati⁶, Ajay Sharma⁷

Affiliations

¹ Laboratory of Peptide Research and Development, School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad & Tobago, West Indies.
² Department of Pharmacy, Faculty of Pharmaceutical Science, Mewar University, Gangrar, Chittorgarh, Rajasthan, India.
³ Department of Pharmaceutical Sciences, USF College of Pharmacy, University of South Florida, Tampa, FL 33612-4749, USA.
⁴ Department of Pharmacogenomics, Bernard J. Dunn School of Pharmacy, Shenandoah University- ICPH Fairfax, Fairfax, VA 22031, USA.
⁵ School of Pharmacy, College of Medicine and Health Sciences, University of Gondar, Gondar 196, Ethiopia.
⁶ Department of Pharmacy, College of Medical and Health Sciences, Wollega University, P.O. Box 395, Nekemte, Ethiopia.
⁷ Department of Pharmacognosy, Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India.

Abstract

A new bioactive proline-rich cyclohexapeptide - diandrine C (6), previously isolated from whole plant of Drymaria diandra (Caryophyllaceae), was synthesized through coupling reactions of tetrapeptide unit Boc-Gly--Pro--Tyr--Trp-OH with dipeptide unit -Pro-Gly-OMe using N,N-diisopropylcarbodiimide (DIPC) as the coupling agent, followed by cyclization of linear hexapeptide unit under alkaline condition. Structure of cyclohexapeptide was confirmed by means of chemical, and spectroscopic analyses and also was screened for its antimicrobial and anthelmintic properties. Bioevaluation results indicated that the newly synthesized hexacyclopeptide exhibited potent antimicrobial activity against Gram-negative bacteria Pseudomonas aeruginosa, Klebsiella pneumoniae and pathogenic Candida albicans at 6 μg/mL. Moderate to good level of antihelmintic activity against three earthworm species Megascoplex konkanensis, Pontoscotex corethruses and Eudrilus eugeniae was also observed at concentration of 2 mg/mL.

Keywords: Antihelmintic activity; Antimicrobial activity; Diandrine C; Drymaria diandra; Proline-rich cyclic peptide; Solution-phase peptide synthesis.