Chiral recognition of metalaxyl enantiomers by human serum albumin: evidence from molecular modeling and photophysical approach

Abstract

Metalaxyl is an acylamine fungicide, belonging to the most widely known member of the amide group. This task is aimed to scrutinize binding region and spatial structural change of principal vector human serum albumin (HSA) complex with (R)-/(S)-metalaxyl by exploiting molecular modeling, steady-state and time-resolved fluorescence, and circular dichroism (CD) approaches. According to molecular modeling, (R)-metalaxyl is situated within subdomains IIA and IIIA and the affinity of site I with (R)-metalaxyl is greater than site II, whereas (S)-metalaxyl is only located at subdomain IIA and the affinity of (S)-metalaxyl with site I is superior compared with that with (R)-metalaxyl. This coincides with the competitive ligand binding, guanidine hydrochloride-induced unfolding of protein, and hydrophobic 8-anilino-1-naphthalenesulfonic acid experiments; the acting forces between (R)-/(S)-metalaxyl and HSA are hydrophobic, π-π interactions, and hydrogen bonds, as derived from molecular modeling. Fluorescence emission manifested that the complex of (R)-/(S)-metalaxyl to HSA is the formation of adduct with an affinity of 10(4) M(-1), which corroborates the time-resolved fluorescence that the static type was operated. Furthermore, the changes of far-UV CD spectra evidence the polypeptide chain of HSA partially unfolded after conjugation with (R)-/(S)-metalaxyl. Through this work, we envisage that it can offer central clues on the biodistribution, absorption, and bioaccumulation of (R)-/(S)-metalaxyl.

Haematological and Biochemical Effects of Metalaxyl Fungicide on Albino Mice

“…There are several areas of concern that need to be extensively investigated. These chemicals are widely used in industry, agriculture, home and gardens for many different purposes, including the protection of seed grain during storage and germination [10]. Individuals who are exposed to these chemicals include agricultural workers, those living in proximity to farms/orchards or consumers who are exposed to pesticide residues in food [5].…”

“…Metalaxyl is a systemic benzenoid fungicide belonging to the most widely known member of the amide group. It is used in foliar spray mixtures for tropical and subtropical crops, as a soil treatment for the control of soil-borne pathogens, and as a seed treatment to control downy mildews, fungal diseases on fruits, cotton, soybeans, peanuts, ornamentals and grasses [10]. Metalaxyl is reported to have hazardous effects on mammalian animals [39].…”

Role of ginger (zingiber officinale) against metalaxyl induced hepatotoxicity in male albino rats: a histological and immunohistochemical study

“…The problems resulting from metalaxyl come from their high residual level in agriculture crops especially vegetables cultivated under greenhouse conditions and doi: 10.7243/2055-091X- [2][3][4][5][6][7][8][9] found that imidaclopride and metalaxyl have genotoxic effects as they induced micronucleus formation in human lymphocytes in vitro and in polychromatic erythrocytes of the rat's bone marrow in vivo.…”

Multispectroscopic and molecular modeling approach to investigate the interaction of diclofop-methyl enantiomers with human serum albumin

“…Consequently, increasing more attention was paid on the molecular mechanisms involved in enantioselective discrimination by HSA. For instance, investigations have shown that enantiomers of warfarin, catechin, ketoprofen, ibuprofen and metalaxyl behave significantly different in pharmacokinetics and interaction with HSA [10][11][12][13][14]. As mentioned above, enantioselectivity in protein binding assessment is a momentous part in the biodistribution of chiral ligands, whereas such consequences cannot be obtained from achiral analysis.…”

“…Peeples et al [31] have investigated the binding of organophosphorus pesticides to commercial albumin protein and indicated there was less physiologically relevant pesticide binding to albumin. Ding et al [13] explored the enantioselective binding of metalaxyl enantiomers to HSA, indicating the binding affinity and binding sites were different between enantiomers. Fig.…”