Modern views on the mechanism of the tuberculostatic action of isonicotinic acid derivatives (a survey of the literature)

1971 ◽  
Vol 5 (6) ◽  
pp. 315-323 ◽  
Author(s):  
T. P. Sycheva
Keyword(s):  
Isonicotinic Acid ◽  
Tuberculostatic Action

Hybrid Design of Isonicotinic Acid Hydrazide Derivatives: Machine Learning Studies, Synthesis and Biological Evaluation of their Antituberculosis Activity

2020 ◽  
Vol 17 (3) ◽  
pp. 365-375
Author(s):  
Vasyl Kovalishyn ◽  
Diana Hodyna ◽  
Vitaliy O. Sinenko ◽  
Volodymyr Blagodatny ◽  
Ivan Semenyuta ◽  
...  
Keyword(s):  
Machine Learning ◽  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Predictive Ability ◽  
Antitubercular Activity ◽  
Biological Evaluation ◽  
Starting Point ◽  
Binary Classifiers ◽  
Synthesis And Biological Evaluation

Background: Tuberculosis (TB) is an infection disease caused by Mycobacterium tuberculosis (Mtb) bacteria. One of the main causes of mortality from TB is the problem of Mtb resistance to known drugs. Objective: The goal of this work is to identify potent small molecule anti-TB agents by machine learning, synthesis and biological evaluation. Methods: The On-line Chemical Database and Modeling Environment (OCHEM) was used to build predictive machine learning models. Seven compounds were synthesized and tested in vitro for their antitubercular activity against H37Rv and resistant Mtb strains. Results: A set of predictive models was built with OCHEM based on a set of previously synthesized isoniazid (INH) derivatives containing a thiazole core and tested against Mtb. The predictive ability of the models was tested by a 5-fold cross-validation, and resulted in balanced accuracies (BA) of 61–78% for the binary classifiers. Test set validation showed that the models could be instrumental in predicting anti- TB activity with a reasonable accuracy (with BA = 67–79 %) within the applicability domain. Seven designed compounds were synthesized and demonstrated activity against both the H37Rv and multidrugresistant (MDR) Mtb strains resistant to rifampicin and isoniazid. According to the acute toxicity evaluation in Daphnia magna neonates, six compounds were classified as moderately toxic (LD50 in the range of 10−100 mg/L) and one as practically harmless (LD50 in the range of 100−1000 mg/L). Conclusion: The newly identified compounds may represent a starting point for further development of therapies against Mtb. The developed models are available online at OCHEM http://ochem.eu/article/11 1066 and can be used to virtually screen for potential compounds with anti-TB activity.

scholarly journals THE ISOLATION AND PROPERTIES OF THE ISONICOTINIC ACID HYDRAZIDE ANALOGUE OF DIPHOSPHOPYRIDINE NUCLEOTIDE

1954 ◽  
Vol 209 (2) ◽  
pp. 467-484 ◽  
Author(s):  
Leonard J. Zatman ◽  
Nathan O. Kaplan ◽  
Sidney P. Colowick ◽  
Margaret M. Ciotti
Keyword(s):  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Isonicotinic Acid Hydrazide

scholarly journals Lysyl oxidase activity and elastin/glycosaminoglycan interactions in growing chick and rat aortas.

1987 ◽  
Vol 105 (3) ◽  
pp. 1463-1469 ◽  
Author(s):  
C Fornieri ◽  
M Baccarani-Contri ◽  
D Quaglino ◽  
I Pasquali-Ronchetti
Keyword(s):  
Hydrophobic Interactions ◽  
Isonicotinic Acid ◽  
Lysyl Oxidase ◽  
Acid Hydrazide ◽  
Elastic Fibers ◽  
Amino Groups ◽  
Lysine Residues ◽  
Oxidase Inhibition

Hydrophobic tropoelastin molecules aggregate in vitro in physiological conditions and form fibers very similar to natural ones (Bressan, G. M., I. Pasquali Ronchetti, C. Fornieri, F. Mattioli, I. Castellani, and D. Volpin, 1986, J. Ultrastruct. Molec. Struct. Res., 94:209-216). Similar hydrophobic interactions might be operative in in vivo fibrogenesis. Data are presented suggesting that matrix glycosaminoglycans (GAGs) prevent spontaneous tropoelastin aggregation in vivo, at least up to the deamination of lysine residues on tropoelastin by matrix lysyl oxidase. Lysyl oxidase inhibitors beta-aminopropionitrile, aminoacetonitrile, semicarbazide, and isonicotinic acid hydrazide were given to newborn chicks, to chick embryos, and to newborn rats, and the ultrastructural alterations of the aortic elastic fibers were analyzed and compared with the extent of the enzyme inhibition. When inhibition was greater than 65% all chemicals induced alterations of elastic fibers in the form of lateral aggregates of elastin, which were always permeated by cytochemically and immunologically recognizable GAGs. The number and size of the abnormal elastin/GAGs aggregates were proportional to the extent of lysyl oxidase inhibition. The phenomenon was independent of the animal species. All data suggest that, upon inhibition of lysyl oxidase, matrix GAGs remain among elastin molecules during fibrogenesis by binding to positively charged amino groups on elastin. Newly synthesized and secreted tropoelastin has the highest number of free epsilon amino groups, and, therefore, the highest capability of binding to GAGs. These polyanions, by virtue of their great hydration and dispersing power, could prevent random spontaneous aggregation of hydrophobic tropoelastin in the extracellular space.

Green route synthesis of 4-thiazolidinone analogs of isonicotinic acid hydrazide

2011 ◽  
Vol 4 (3) ◽  
pp. 211-217 ◽  
Author(s):  
Asha B. Thomas ◽  
Piyoosh A. Sharma ◽  
Preeti N. Tupe ◽  
Ravindra V. Badhe ◽  
Rabindra K. Nanda ◽  
...  
Keyword(s):  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Isonicotinic Acid Hydrazide ◽  
Green Route

An HPLC screening method for the detection of isonicotinic acid hydrazide in cattle milk

1995 ◽  
Vol 40 (3-4) ◽  
pp. 170-174 ◽  
Author(s):  
A. Defilippi ◽  
G. Piancone ◽  
R. Costa Laia ◽  
G. P. Tibaldi
Keyword(s):  
Isonicotinic Acid ◽  
Screening Method ◽  
Acid Hydrazide ◽  
Isonicotinic Acid Hydrazide

Adsorption and Charge-Transfer Study of Bi-isonicotinic Acid on In Situ-Grown Anatase TiO2Nanoparticles

2004 ◽  
Vol 108 (10) ◽  
pp. 3114-3122 ◽  
Author(s):  
Joachim Schnadt ◽  
Anders Henningsson ◽  
Martin P. Andersson ◽  
Patrik G. Karlsson ◽  
Per Uvdal ◽  
...  
Keyword(s):  
Charge Transfer ◽  
Isonicotinic Acid ◽  
Transfer Study

scholarly journals The comparative study of linear solvatation energy relationship for the reactivity of pyridine carboxylic acids with diazodiphenylmethane in protic and aprotic solvents

2012 ◽  
Vol 77 (10) ◽  
pp. 1311-1338 ◽  
Author(s):  
Sasa Drmanic ◽  
Jasmina Nikolic ◽  
Aleksandar Marinkovic ◽  
Bratislav Jovanovic
Keyword(s):  
Solvent Effects ◽  
Kinetic Data ◽  
Aprotic Solvent ◽  
Isonicotinic Acid ◽  
Linear Regression Analysis ◽  
Multiple Linear Regression Analysis ◽  
Reaction Rates ◽  
Aprotic Solvents ◽  
Pyridine Carboxylic ◽  
The Comparative Study

Protic and aprotic solvent effects on the reactivity of picolinic, nicotinic and isonicotinic acid, as well as of some substituted nicotinic acids with diazodiphenylmethane (DDM) were investigated. In order to explain the kinetic results through solvent effects, the second-order rate constants for the reaction of the examined acids with DDM were correlated using the Kamlet-Taft solvatochromic equation. The correlations of the kinetic data were carried out by means of the multiple linear regression analysis and the solvent effects on the reaction rates were analyzed in terms of the contributions of the initial and the transition state. The signs of the equation coefficients support the already known reaction mechanism. The solvatation models for all the investigated acids are suggested and related to their specific structure.

Acetylation of procainamide in man and its relationship to isonicotinic acid hydrazide acetylation phenotype

1975 ◽  
Vol 17 (4) ◽  
pp. 395-399 ◽  
Author(s):  
Thomas P. Gibson ◽  
Jean Matusik ◽  
Edward Matusik ◽  
Howard A. Nelson ◽  
Joanne Wilkinson ◽  
...  
Keyword(s):  
Isonicotinic Acid ◽  
Acid Hydrazide ◽  
Isonicotinic Acid Hydrazide ◽  
Acetylation Phenotype
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