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

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.

Figure 1

Chemical structures of compounds isolated in the current study from the stem bark of Erythrina lysistemon. erybraedin A (1), phaseollidin (2), abyssinone V-4’ methyl ether (3), eryzerin C (4), alpumisoflavone (5), cristacarpin (6) and lysisteisoflavone (7).

Figure 2

Discriminating Klekota-Roth fragments identified by the decision tree. The fragments were selected by the decision tree to discriminate the four classes of activity (A, B, C and D). The ‘A’ symbol in chemical structures indicates an atom that is not hydrogen (e.g., carbon or oxygen), and hydrogen atoms (whether shown or implied). The ‘AH’ symbol indicates an atom can be hydrogen, carbon or oxygen. Arrows indicate the presence of a particular fragment and dotted arrows indicate its absence. The nodes that contain the fragments are classified and sequential. The fraction of active compounds is listed on each end node (e.g., Class A, was found on four end nodes: A1, A2, A3 and A4 (Section 2.4)).

Figure 3

Structure activity relationship (SAR) predicted class A structures: This gave a similar class prediction as compared to QSAR predicted, which gave 77% accuracy (Figure 7).

Figure 4

SAR predicted class B structures: This gave a similar class prediction as compared to QSAR predicted, which gave 77% accuracy (Figure 7).

Figure 5

SAR predicted class C structures: This gave a similar class prediction as compared to QSAR predicted, which gave 77% accuracy (Figure 7).

Figure 6

SAR predicted class D structures: This gave a similar class prediction as compared to QSAR predicted, which gave 77% accuracy (Figure 7).

Figure 7

Plot of predicted versus experimental pMIC values for Pace Regression model.