Latest Research News on Hydroxamic Acids : March – 2020

The Chemistry of Hydroxamic Acids and N‐Hydroxyimides

This progress report is concerned primarily with problems relating to the structure and reactions of hydroxamic acids and N‐hydroxyimides, and also surveys some of the biological activities of these compounds. Particular significance attaches to the Lossen rearrangement of O‐acylated hydroxamic acids, which leads to isocyanates or their reaction products. [1]

Hydroxamic Acids as Pharmacological Agents

A variety of hydroxamic acid derivatives have recently been touted for their potential use as inhibitors of hypertension, tumor growth, inflammation, infectious agents, asthma, arthritis, and more. Here we provide a comprehensive review of the basic medicinal chemistry and pharmacology of hydroxamic acid derivatives that have been examined as inhibitors of zinc metalloproteases, matrix metalloproteinases, leukotriene A4 hydrolases, ureases, lipoxigenases, cyclooxygenases, as well as peptide deformilases. [2]

Specific Inhibition of the Cyanide-insensitive Respiratory Pathway in Plant Mitochondria by Hydroxamic Acids

Hydroxamic acids, R-CONHOH, are inhibitors specific to the respiratory pathway through the alternate, cyanide-insensitive terminal oxidase of plant mitochondria. The nature of the R group in these compounds affects the concentration at which the hydroxamic acids are effective, but it appears that all hydroxamic acids inhibit if high enough concentrations are used. [3]

Prediction of the Inhibitory Concentration of Hydroxamic Acids by DFT-QSAR Models on Histone Deacetylase 1

In order to study the relationship between inhibitory concentration and the molecular structures of hydroxamic acids, a Quantitative Structure Activity Relationship (QSAR) study is applied to a set of 31 histone deacetylase inhibitors (HDACi). This study is performed by using the Principal Component Analysis (PCA) method, the Ascendant Hierarchical Classification (AHC), the Linear Multiple Regression Method (RML) and the nonlinear regression (RMNL). Multivariate statistical analysis allowed to obtain two quantitative models (RML model and RMNL model) by the means of the quantum descriptors those are the dipole moment (μ), the bond length d(C=O) and the valence angles α°(O=C-N) and α°(H-N-O). The RMNL model gives statistically significant results and shows a good predictability R2 = 0.967, S = 0.379 and F = 557.031. The valence angle α°(O=C-N) is the priority descriptor in the prediction of the inhibitory concentration of the studied hydroxamic acids. The obtained results show that geometric descriptors could be useful for predicting the inhibitory concentration of histone deacetylase inhibitors. [4]

Synthesis, Characterization, DNA Binding, Antibacterial Activity and DFT Calculation of Ru(II) Complexes of Hydroxamic Acids and 1,10Phenanthroline

New Ruthenium (II) complexes of mixed ligands, hydroxamic acid (L1 = AHA (acetohydroxamic acid) and L2 = BHA (benzohydroxamic acid)) and 1, 10-phenanthroline (phen) were synthesized, characterized by FT-infra red spectrophotometer, UV-visible spectrometer, ESI-mass spectrometer and elemental analysis. In the complexes, [Ru(phen)2L] (L = AHA, BHA), the metal ion is bind with 6 atoms, 2 O-atoms from hydroxamic acids (AHA & BHA) and 4 N-atoms from 1, 10-phenanthroline to form octahedral Ruthenium (II) complexes. The binding of these complexes with CT-DNA has been studied by UV-visible spectrophotometer. The DNA-binding coefficients for complexes [Ru(phen)2AHA]  and [Ru(phen)2BHA] are 2.29 x 106 M-1 and 3.30 x 106 M-1 respectively. Detailed study indicates that these complexes bind with DNA by intercalation binding. Also studied microbial [5]

Reference

[1] Bauer, L. and Exner, O., 1974. The chemistry of hydroxamic acids and N‐hydroxyimides. Angewandte Chemie International Edition in English13(6), pp.376-384.

[2] Muri, E.M., Nieto, M.J., Sindelar, R.D. and Williamson, J.S., 2002. Hydroxamic acids as pharmacological agents. Current Medicinal Chemistry9(17), pp.1631-1653.

[3] Schonbaum, G.R., Bonner, W.D., Storey, B.T. and Bahr, J.T., 1971. Specific inhibition of the cyanide-insensitive respiratory pathway in plant mitochondria by hydroxamic acids. Plant Physiology47(1), pp.124-128.

[4] Soro, D., Ekou, L., Koné, M.G.R., Ekou, T., Affi, S.T., Ouattara, L. and Ziao, N., 2018. Prediction of the inhibitory concentration of hydroxamic acids by DFT-QSAR models on histone deacetylase 1. International Research Journal of Pure and Applied Chemistry, pp.1-13.

[5] Sahu, R.K. and Khan, F., 2016. Synthesis, Characterization, DNA Binding, Antibacterial Activity and DFT Calculation of Ru (II) Complexes of Hydroxamic Acids and 1, 10-Phenanthroline. Chemical Science International Journal, pp.1-11.

 

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