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

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

Maia Merlani  1 , Dieter M Scheibel  2 , Vakhtang Barbakadze  1 , Lali Gogilashvili  1 , Lela Amiranashvili  1 , Athina Geronikaki  3 , Valentina Catania  4 , Domenico Schillaci  4 , Giuseppe Gallo  5 , Ivan Gitsov  2   6   7
Affiliations

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

Maia Merlani et al. Pharmaceutics. .

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].

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
(a) Comfrey (S. officinale) plant leaves and flower. This file is licensed under the Creative Commons Attribution-Share Alike 3.0 Unported. credit to: User: Aiwok/Wikimedia Commons/CC-BY-SA-3.0 [6] (b) A. Italica (roots). Source: A voucher specimen TBPH-224 of A.italica is deposited in the Herbarium of the Institute of Pharmacochemistry, Tbilisi State Medical University (TSMU), Tbilisi, Georgia. (c) S. caucasicum. Source: A voucher specimen TBPH-20996 of S. caucasicum is deposited in the Herbarium of the Institute of Pharmacochemistry, TSMU, Tbilisi, Georgia.
Figure 2
Figure 2
Poly[3-(3,4-dihydroxyphenyl)glyceric acid] (PDHPGA) (1) and poly[2-methoxycarbonyl-3-(3,4-dihydroxyphenyl)oxirane] (PMDHPO) (2).
Figure 3
Figure 3
2-methoxycarbonyl-3-(3,4-dimethoxyphenyl)oxirane (MDMPO) (3), 2-methoxycarbonyl-3-(3,4-dibenzyloxyphenyl)-oxirane (MDBPO) (4), 2-benzyloxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane (BDBPO) (5), 2-t-butyloxycarbonyl-3-(3,4-dibenzyloxyphenyl)oxirane (TBDBPO) (6).
Scheme 1
Scheme 1
Enzymatic polymerization of MDBPO and modification of the polymer: (a) C. rugosa lipase, toluene, 80 °C, 7 days (b) Pd/C, H2, THF/EtOH.
Figure 4
Figure 4
SEC traces of MDBPO monomer (1, green trace) and polymer PMDBPO (2, black trace). X—internal standard. See experimental for analysis conditions.
Figure 5
Figure 5
MALDI-TOF mass spectrum of PMDBPO. See experimental for analysis conditions.
See this image and copyright information in PMC

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