Pyrazole derivatives as antileishmanial agents: Biological evaluation, molecular docking study, DFT analysis and ADME prediction.

Leishmaniasis is a parasitic disease that is commonly found in tropical and sub-tropical regions. Currently, there is no protective antileishmanial vaccine, and the available clinical drugs have serious side effects. On the other hand, due to the emergence of multidrug-resistant strains of the causative pathogens, the study and design of novel antileishmanial agents is urgently needed.

Synthesis, biological evaluation, molecular docking, MD simulation and DFT analysis of new 3-hydroxypyridine-4-one derivatives as anti-tyrosinase and antioxidant agents.

In the present study, ten new substituted 3-hydroxypyridine-4-one derivatives were synthesized in a four-step method, and their chemical structures were confirmed using various spectroscopic techniques. Subsequently, the inhibitory activities of these derivatives against tyrosinase enzyme and their antioxidant activities were evaluated. Amongest the synthesized compounds, bearing a 4-OH-3-OCH substitution was found to be a promising tyrosinase inhibitor with an IC value of 25.

New 3-Hydroxypyridine-4-one Analogues: Their Synthesis, Antimicrobial Evaluation, Molecular Docking, and ADME Prediction.

Introduction: Drug resistance to existing antimicrobial drugs has become a serious threat to human health, which highlights the need to develop new antimicrobial agents.

Methods: In this study, a new set of 3-hydroxypyridine-4-one derivatives (6a-j) was synthesized, and the antimicrobial effects of these derivatives were evaluated against a variety of microorganisms using the microdilution method. The antimicrobial evaluation indicated that compound 6c, with an electron-donating group -OCH at the meta position of the phenyl ring, was the most active compound against and species with an MIC value of 32 μg/mL.

Synthesis, design, biological evaluation, and computational analysis of some novel uracil-azole derivatives as cytotoxic agents.

The design and synthesis of novel cytotoxic agents is still an interesting topic for medicinal chemistry researchers due to the unwanted side effects of anticancer drugs. In this study, a novel series of uracil-azole hybrids were designed and synthesized. The cytotoxic activity, along with computational studies: molecular docking, molecular dynamic simulation, density functional theory, and ADME properties were also, evaluated.

Synthesis of 3-hydroxypyridin-4-one derivatives bearing benzyl hydrazide substitutions towards anti-tyrosinase and free radical scavenging activities.

Tyrosinase is a vital enzyme in the biosynthesis of melanin, which has a significant role in skin protection. Due to the importance of the tyrosinase enzyme in the cosmetics and health industries, studies to design new tyrosinase inhibitors have been expanded. In this study, the design and synthesis of 3-dihydroxypyridine-4-one derivatives containing benzo hydrazide groups with different substitutions were carried out, and their antioxidant and anti-tyrosinase activities were also evaluated.

Design, synthesis, ADME, DFT, molecular dynamics simulation, anti-tyrosinase, and antioxidant activity of some of the 3-hydroxypyridin-4-one hybrids in combination with acylhydrazone derivatives.

Tyrosinase is the rate-limiting enzyme in synthesizing melanin. Melanin is responsible for changing the color of fruits and vegetables and protecting against skin photo-carcinogenesis. Herein, some of the hybrids of 3-hydroxypyridine-4-one and acylhydrazones were designed and synthesized to study the anti-tyrosinase and antioxidant activities.

Comparison of Protective Effects of Phenolic Acids on Protein Glycation of BSA Supported by In Vitro and Docking Studies.

Several diabetic complications are associated with forming advanced glycation end products (AGEs). Different chemical and natural compounds are able to prevent the development of these products. In this study, glycosylation was induced as a model by incubating bovine serum albumin (BSA) with glucose.

Quinazoline analogues as cytotoxic agents; QSAR, docking, and studies.

Background And Purpose: Synthesis and investigation of pharmacological activity of novel compounds are time and money-consuming. However, computational techniques, docking, and studies have facilitated drug discovery research to design pharmacologically effective compounds.

Experimental Approach: In this study, a series of quinazoline derivatives were applied to quantitative structure-activity relationship (QSAR) analysis.

Synthesis of some novel dibromo-2-arylquinazolinone derivatives as cytotoxic agents.

Recently the quinazoline derivatives have attracted much attention for their anticancer properties. In this study a series of new brominated quinazoline derivatives () were synthesized in two steps. In the first step we used N-bromosuccinimide to brominate the anthranilamid.

Novel Catechol Derivatives of Arylimidamides as Antileishmanial Agents.

Two novel bis-arylimidamide derivatives with terminal catechol moieties (9a and 10a) and two parent compounds with terminal phenyl groups (DB613 and DB884) were synthesized as dihydrobromide salts (9b and 10b). The designed compounds were hybrid molecules consisting of a catechol functionality embedded in an arylimidamide moiety. All compounds were examined for in vitro antiparasitic activity upon promastigotes of Leishmania major and L.

Computer-aided design of novel antibacterial 3-hydroxypyridine-4-ones: application of QSAR methods based on the MOLMAP approach.

3-Hydroxypyridine-4-one derivatives have shown good inhibitory activity against bacterial strains. In this work we report the application of MOLMAP descriptors based on empirical physicochemical properties with genetic algorithm partial least squares (GA-PLS) and counter propagation artificial neural networks (CP-ANN) methods to propose some novel 3-hydroxypyridine-4-one derivatives with improved antibacterial activity against Staphylococcus aureus. A large collection of 302 novel derivatives of this chemical scaffold was selected for this purpose.

QSAR study of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2 using LS-SVM and GRNN based on principal components.

Quantitative relationships between molecular structure and methionine aminopeptidase-2 inhibitory activity of a series of cytotoxic anthranilic acid sulfonamide derivatives were discovered. We have demonstrated the detailed application of two efficient nonlinear methods for evaluation of quantitative structure-activity relationships of the studied compounds. Components produced by principal component analysis as input of developed nonlinear models were used.

QSAR study of isatin analogues as in vitro anti-cancer agents.

Quantitative structure activity relationships (QSAR) of anti-cancer isatin derivatives were discovered by multiple linear regressions (MLR) and genetic algorithm partial least squares (GA-PLS) methods. Topological, chemical, geometrical and functional groups descriptors were found to be effective parameters on the cytotoxic activity. The positive effects of the number of halogen atoms and the number of total secondary carbons, and the negative effects of the number of secondary amides, and the number of ketones on the anti-cancer activity were in agreement with previous SAR studies.

Quantitative structure-activity relationship studies on 2-amino-6-arylsulfonylbenzonitriles as human immunodeficiency viruses type 1 reverse transcriptase inhibitors using descriptors obtained from substituents and whole molecular structures.

The human immunodeficiency viruses type 1 reverse transcriptase is a major target for drug development. Inhibition of this enzyme has been one of the primary therapeutic strategies in suppressing the replication of human immunodeficiency viruses type 1. A series of 2-amino-6-arylsulfonylbenzonitrile derivatives was subjected to quantitative structure-activity relationship analysis.

QSAR study of PETT derivatives as potent HIV-1 reverse transcriptase inhibitors.

A series of phenylethylthiazolylthiourea (PETT) derivatives was subjected to quantitative structure-activity relationship (QSAR) analysis to find the structural requirements for ligand binding. The structural invariants used in this study were those obtained from whole molecular structures: chemical, quantum, topological, geometrical, constitutional and functional groups. Four chemometrics methods including multiple linear regressions (MLRs), factor analysis-MLR (FA-MLR), principal component regression analysis (PCRA) and partial least squares combined with genetic algorithm for variable selection (GA-PLS) were employed to make connections between structural parameters and enzyme inhibition.

Synthesis and antitubercular activity of novel 4-substituted imidazolyl-2,6-dimethyl-N3,N5-bisaryl-1,4-dihydropyridine-3,5-dicarboxamides.

A series of 4-substituted imidazolyl-2,6-dimethyl-N(3),N(5)-bisaryl-1,4-dihydropyridine-3,5-dicarboxamides were prepared. They were screened as antitubercular agents against Mycobacterium tuberculosis H(37)Rv. Minimum inhibitory concentrations (MICs) were determined using agar proportion method.

QSAR study of antimicrobial 3-hydroxypyridine-4-one and 3-hydroxypyran-4-one derivatives using different chemometric tools.

A series of 3-hydroxypyridine-4-one and 3-hydroxypyran-4-one derivatives were subjected to quantitative structure-antimicrobial activity relationships (QSAR) analysis. A collection of chemometrics methods, including factor analysis-based multiple linear regression (FA-MLR), principal component regression (PCR) and partial least squares combined with genetic algorithm for variable selection (GA-PLS) were employed to make connections between structural parameters and antimicrobial activity. The results revealed the significant role of topological parameters in the antimicrobial activity of the studied compounds against S.

QSAR study of p56(lck) protein tyrosine kinase inhibitory activity of flavonoid derivatives using MLR and GA-PLS.

Quantitative relationships between molecular structure and p56(lck) protein tyrosine kinase inhibitory activity of 50 flavonoid derivatives are discovered by MLR and GA-PLS methods. Different QSAR models revealed that substituent electronic descriptors (SED) parameters have significant impact on protein tyrosine kinase inhibitory activity of the compounds. Between the two statistical methods employed, GA-PLS gave superior results.

Synthesis, antimicrobial evaluation and QSAR study of some 3-hydroxypyridine-4-one and 3-hydroxypyran-4-one derivatives.

A series of Mannich bases of 2-alkyl-3-hydroxy-pyridine-4-ones, namely 2-alkyl-3-hydroxy-5-N-piperidylmethyl or N,N-dialkylaminomethyl pyridine-4-ones 9, 10 and 15-18, two derivatives of N-aryl-2-methyl-3-hydroxy-pyridine-4-ones 19, 20 and two N-alkyl derivatives of maltol, 21 and 22 were prepared. They were screened for their antibacterial and antifungal activities against a variety of microorganisms using micro plate Alamar Blue((R)) assay (MABA) method. Multiple linear regressions (MLR) analysis was performed for the synthesized compounds as well as a series of pyridinone and pyranone derivatives 23-43 which have been synthesized and evaluated for antimicrobial activity by other researchers previously.