Effects of isatin‐isoniazid derivatives on drug metabolizing and chemoprotective enzymes in mice

El‐Sayed, Wael M.; Aboul‐Fadl, Tarek; Franklin, Michael R.

doi:10.1002/ddr.20376

Cited by 5 publications

(4 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…El Sayed’s group analyzed the influence of some isoniazid derivatives on the expression of mRNA and activity of enzymes implicated in drug metabolism in mice [ 54 ]. Although the analyzed compounds determined some changes in mRNA expressions, their influence on enzymes activity was minor [ 54 ]. The increased expression levels of CYP1A1 induced by the new synthesized isoniazid derivatives could be explained by the induction of their metabolism.…”

Section: Resultsmentioning

confidence: 99%

“…The treatment of HT-29 cells with 50 μg/mL of compound 7 has no toxic effect after 24 h, but after 48 and 72 h it induced necrosis in 28.6% and 54%, respectively, of Isoniazid inhibits CYP2C19 and CYP3A4 activities and mechanistically inactivates CYP1A2, CYP2A6, CYP2C19, and CYP3A4 in human liver microsomes [52,53]. El Sayed's group analyzed the influence of some isoniazid derivatives on the expression of mRNA and activity of enzymes implicated in drug metabolism in mice [54]. Although the analyzed compounds determined some changes in mRNA expressions, their influence on enzymes activity was minor [54].…”

Section: Cytotoxicity and Effects On Cell Cyclementioning

confidence: 99%

See 1 more Smart Citation

Synthesis, Characterization, and Biologic Activity of New Acyl Hydrazides and 1,3,4-Oxadiazole Derivatives

et al. 2020

View full text Add to dashboard Cite

Starting from isoniazid and carboxylic acids as precursors, thirteen new hydrazides and 1,3,4-oxadiazoles of 2-(4-substituted-phenoxymethyl)-benzoic acids were synthesized and characterized by appropriate means. Their biological properties were evaluated in terms of apoptosis, cell cycle blocking, and drug metabolism gene expression on HCT-8 and HT-29 cell lines. In vitro antimicrobial tests were performed by the microplate Alamar Blue assay for the anti-mycobacterial activities and an adapted agar disk diffusion technique for other non-tubercular bacterial strains. The best antibacterial activity (anti-Mycobacterium tuberculosis effects) was proved by 9. Compounds 7, 8, and 9 determined blocking of G1 phase. Compound 7 proved to be toxic, inducing apoptosis in 54% of cells after 72 h, an effect that can be predicted by the increased expression of mRNA caspases 3 and 7 after 24 h. The influence of compounds on gene expression of enzymes implicated in drug metabolism indicates that synthesized compounds could be metabolized via other pathways than NAT2, spanning adverse effects of isoniazid. Compound 9 had the best antibacterial activity, being used as a disinfectant agent. Compounds 7, 8, and 9, seemed to have antitumor potential. Further studies on the action mechanism of these compounds on the cell cycle may bring new information regarding their biological activity.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Cytotoxicity and Effects On Cell Cyclementioning

confidence: 99%

Synthesis, Characterization, and Biologic Activity of New Acyl Hydrazides and 1,3,4-Oxadiazole Derivatives

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Conjugating INH and isatin is a promising strategy to search potential anti‐TB candidates because the increased lipophilicity may increase drug permeability and allow drugs to get into bacterial cells. Several isatin‐ INH hybrids linked by hydrazone were assessed for their anti‐TB activities, and some of them showed preeminent activities against MTB H37Rv . All 41 displayed excellent anti‐TB activities with MIC of 3.5–4.5 μg/mL against MTB, which were as potent as the parent drug INH (MIC: 1.5 μg/mL).…”

Section: Isatin‐(thio)hydrazone Hybridsmentioning

confidence: 99%

Isatin Derivatives with Potential Antitubercular Activities

Jiang

Wang

Liu

et al. 2018

Journal of Heterocyclic Chem

View full text Add to dashboard Cite

Tuberculosis is a life‐threatening chronic infectious disease, which primarily affects the lungs but can spread to other vital organs. The re‐emergence and wide spread of new virulent forms of Mycobacterium tuberculosis that are resistant to some or all first and second line antitubercular agents has reached an alarming level in recent decades. Thus, it is imperative to develop more effective agents. Isatin derivatives are endowed with diverse biological properties, therefore thousands of isatin derivatives have been synthesized in hopes of discovering new candidates with potential antitubercular activities against both drug‐susceptible and drug‐resistant strains. This review summarizes the recent developments of isatin derivatives with potential antitubercular activities.

show abstract

“…These characteristics demonstrate the potential for development as an antitubercular agent, as observed with derivatives containing hydrazone group (-C=N-NH-R) [26,27]. Aboul-fadl and co-workers synthesized 5-fluoroisatin isoniazid hydrazone derivatives from isatin and isoniazid with promising activity against M. tuberculosis H37Rv (MIC 0.035 mM) [19], and despite the potential application, only a few studies have been reported [1,28,29]. A previous study indicated 5,7-dibromoisatin based hydrazone derivatives have lower MIC value than parent drugs [30].…”

Section: Introductionmentioning

confidence: 99%

Isoniazid-Isatin Hydrazone Derivatives: Synthesis, Antitubercular Activity and Molecular Docking Studies

et al. 2021

View full text Add to dashboard Cite

This study examined the synthesis of isoniazid-isatin hydrazone derivatives 5-7, followed by an investigation on the in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, and molecular docking. A yield of 81 - 92 % of these compounds was achieved, with structural characterization by spectroscopic methods (FTIR, NMR, HRMS). The in vitro antitubercular activity was evaluated against M. tuberculosis H37Rv, and the highest effect was observed in compound 7, with a minimum inhibitory concentration (MIC) of 0.017 mM, lower than rifampicin (MIC 0.048 mM), which served as the positive control. In addition, the molecular docking of 5-7 was performed to visualize the interaction of isoniazid-isatin hydrazone derivatives with the active site of InhA receptor, which was in agreement with the experimental data. The hydrogen bonding with Ser94 and pi-pi interaction with Phe41 and/or Phe97 on the InhA active site was pivotal for the antitubercular activity. HIGHLIGHTS Tuberculosis caused by Mycobacterium tuberculosis is one of the top ten leading causes of death globally The first and second lines of antituberculosis drugs are the prevalent treatment for this disease, but they show several drawbacks and are exacerbated by the occurrence of drug resistance The isoniazid-isatin hydrazone derivatives were designed through molecular hybridization and synthesized effectively and exhibited moderate to high activity against tuberculosis H37Rv Molecular docking study demonstrated that the hydrogen bonding with Ser94 and the pi-pi interaction with Phe41 and/or Phe97 are important for antitubercular activity GRAPHICAL ABSTRACT

show abstract

Effects of isatin‐isoniazid derivatives on drug metabolizing and chemoprotective enzymes in mice

Cited by 5 publications

References 48 publications

Synthesis, Characterization, and Biologic Activity of New Acyl Hydrazides and 1,3,4-Oxadiazole Derivatives

Synthesis, Characterization, and Biologic Activity of New Acyl Hydrazides and 1,3,4-Oxadiazole Derivatives

Isatin Derivatives with Potential Antitubercular Activities

Isoniazid-Isatin Hydrazone Derivatives: Synthesis, Antitubercular Activity and Molecular Docking Studies

Contact Info

Product

Resources

About