Antimicrobial Isoflavones and Derivatives from Erythrina (Fabaceae): Structure Activity Perspective (Sar & Qsar) on Experimental and Mined Values Against Staphylococcus Aureus

Nicholas J Sadgrove; Tiago B Oliveira; Gugulethu P Khumalo; Sandy F van Vuuren; Ben-Erik van Wyk

doi:10.3390/antibiotics9050223

Antimicrobial Isoflavones and Derivatives from Erythrina (Fabaceae): Structure Activity Perspective (Sar & Qsar) on Experimental and Mined Values Against Staphylococcus Aureus

Antibiotics (Basel). 2020 Apr 30;9(5):223. doi: 10.3390/antibiotics9050223.

Authors

Nicholas J Sadgrove^{1

2}, Tiago B Oliveira³, Gugulethu P Khumalo², Sandy F van Vuuren⁴, Ben-Erik van Wyk²

Affiliations

¹ Jodrell Science Laboratory, Royal Botanic Gardens, Kew, Richmond, Surrey TW9 3AB, UK.
² Department of Botany and Plant Biotechnology, University of Johannesburg, P.O. Box 524, Auckland Park 2006, South Africa.
³ Department of Pharmacy, Federal University of Sergipe (UFS-SE), São Cristóvão 491000-000, Brazil.
⁴ Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand, 7 York Road, Park town 2193, South Africa.

Abstract

Prenylated (iso)flavonoids, -flavans and pterocarpans from taxa in Erythrina are repeatedly flagged as potent antimicrobial compounds. In the current study, bark from E. lysistemon was extracted and seven isoflavone derivatives were purified: erybraedin A (1), phaseollidin (2), abyssinone V-4' methyl ether (3), eryzerin C (4), alpumisoflavone (5), cristacarpin (6) and lysisteisoflavone (7). Minimum inhibition concentration (MIC) values were determined against a range of species of bacteria (skin pathogens), then values for another 67 derivatives from Erythrina, only against Staphylococcus aureus, were mined from the literature. Of the seven isolates, MIC values widely ranged from 1-600 μg/mL, with no obvious pattern of selectivity for Gram-types. Nevertheless, using the mined and experimentally determined values against S. aureus, Klekota-Roth fragments (Structure Activity Relationship: SAR) were determined then used as molecular descriptors to make a 'decision tree' based on structural characters inspired by the classes of antimicrobial potency (classes A-D). Furthermore, to make quantitative predictions of MIC values (Quantitative SAR: QSAR) 'pace regression' was utilized and validated (R² = 0.778, Q² = 0.727 and P² = 0.555). Evidently, the position and degree of prenylation is important; however, the presence of hydroxyl groups at positions 5 and 7 in ring A and 4' in ring B is associated with lower MIC values. While antimicrobial results continue to validate the traditional use of E. lysistemon extracts (or Erythrina generally) in therapeutic applications consistent with anti-infection, it is surprising that this class of compound is not being utilized more often in general industry applications, such as food or cosmetic preservation, or in topical antimicrobial creams. Prenylated (iso)flavonoids are derived from several other Genera, such as Dorstenia (Moraceae), Ficus (Moraceae), Glycyrrhiza (Fabaceae), Paulownia (Lamiales) or Pomifera (Moraceae).

Keywords: MRSA; QSAR; prenylated isoflavonoid; pterocarpan; traditional medicine.