Enzymatic Synthesis and Antimicrobial Activity of Oligomer Analogues of Medicinal Biopolymers from Comfrey and Other Species of the Boraginaceae Family

Maia Merlani; Dieter M Scheibel; Vakhtang Barbakadze; Lali Gogilashvili; Lela Amiranashvili; Athina Geronikaki; Valentina Catania; Domenico Schillaci; Giuseppe Gallo; Ivan Gitsov

doi:10.3390/pharmaceutics14010115

Enzymatic Synthesis and Antimicrobial Activity of Oligomer Analogues of Medicinal Biopolymers from Comfrey and Other Species of the Boraginaceae Family

Pharmaceutics. 2022 Jan 4;14(1):115. doi: 10.3390/pharmaceutics14010115.

Authors

Affiliations

¹ Kutateladze Institute of Pharmacochemistry, Tbilisi State Medical University, 36 P.Sarajishvili Street, 0159 Tbilisi, Georgia.
² Department of Chemistry, College of Environmental Science and Forestry, State University of New York, 1 Forestry Drive, Syracuse, NY 13210, USA.
³ School of Pharmacy, Aristotle University, 54124 Thessaloniki, Greece.
⁴ Laboratory of Microbiology and Biologic Assays, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, 32 Via Archirafi, 90123 Palermo, Italy.
⁵ Laboratory of Molecular Microbiology and Biotechnology, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Viale delle Scienze, ed. 16, 90128 Palermo, Italy.
⁶ The Michael M. Szwarc Polymer Research Institute, Syracuse, NY 13210, USA.
⁷ The BioInspired Institute, Syracuse University, Syracuse, NY 13210, USA.

Abstract

This study reports the first enzymatic synthesis leading to several oligomer analogues of poly[3-(3,4-dihydroxyphenyl)glyceric acid]. This biopolymer, extracted from plants of the Boraginaceae family has shown a wide spectrum of pharmacological properties, including antimicrobial activity. Enzymatic ring opening polymerization of 2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane (MDBPO) using lipase from Candida rugosa leads to formation of poly[2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane] (PMDBPO), with a degree of polymerization up to 5. Catalytic debenzylation of PMDBPO using H₂ on Pd/C yields poly[2-methoxycarbonyl-3-(3,4-dihydroxyphenyl)oxirane] (PMDHPO) without loss in molecular mass. Antibacterial assessment of natural polyethers from different species of Boraginaceae family Symhytum asperum, S. caucasicum,S. grandiflorum, Anchusa italica, Cynoglossum officinale, and synthetic polymers, poly[2-methoxycarbonyl-3-(3,4-dimethoxyphenyl)oxirane (PMDMPO) and PMDHPO, reveals that only the synthetic analogue produced in this study (PMDHPO) exhibits a promising antimicrobial activity against pathogenic strains S.aureus ATCC 25923 and E.coli ATCC 25922 the minimum inhibitory concentration (MIC) being 100 µg/mL.

Keywords: Boraginaceae family; antimicrobial activity; enzymatic polymerization; lipase; poly[3-(3,4-dihydroxyphenyl)glyceric acid].

Grants and funding

FFR-D15-001709/University of Palermo