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A new series of N?-(substituted phenyl)-5-chloro/iodo-3-phenyl-1H-indole-2-carbohydrazide (5, 6) and N-[2-(substituted phenyl)-4-oxo-1,3-thiazolidin-3-yl]-5-iodo/chloro-3-phenyl-1H-indole-2-carboxamide (7, 8) derivatives were synthesized and evaluated for their anticancer properties. Compounds 5a and 6b, selected as prototypes by the National Cancer Institute for screening against the full panel of 60 human tumor cell lines at a minimum of five concentrations at 10-fold dilutions, demonstrated remarkable antiproliferative activity against leukemia, non-small cell lung cancer, colon cancer, central nervous system (CNS) cancer, melanoma, ovarian cancer, renal cancer, and breast cancer (MCF-7) cell lines with GI50 values < 0.4 muM. A subset of the compounds was then tested for their potential to inhibit tubulin polymerization. Compounds 6f and 6g showed significant cytotoxicity at the nM level on MCF-7 cells and exhibited significant inhibitory activity on tubulin assembly and colchicine binding at about the same level as combretastatin A-4. Finally, docking calculations were performed to identify the binding mode of these compounds. Group 5 and 6 compounds interacted with the colchicine binding site through hydrophobic interactions similar to those of colchicine. These compounds with antiproliferative activity at high nanomolar concentration can serve as scaffolds for the design of novel microtubule targeting agents. Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.Reference of 2682-49-7. In my other articles, you can also check out more blogs about 2682-49-7

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Background: Acquired immunodeficiency Syndrome (AIDS) is caused by Human immunodeficiency virus type 1 (HIV-1). Pyrazine and Thiazolidinone pharmacophore has diverse biological activities including anti HIV activity. Aims and Objectives: To study binding behavior of Pyrazine-thiazolidinone derivatives on four different crystal structures of HIV-1RT.These molecules which were already reported as anti-TB were investigated for dual activity as Anti-HIV and Anti-TB. Materials and Methods: In the present study we describe a comparative docking study of twenty-three derivatives of N-(4-oxo-2 substituted thiazolidin-3-yl) pyrazine-2-carbohydrazide. Binding pattern of these derivatives was gauged by molecular docking studies on four different receptors bearing PDB code 1ZD1, 1RT2, 1FKP and 1FK9 of HIV?RT enzyme using V. Life MDS software Genetic algorithm docking method. Result and Discussion: The studies revealed hydrogen bonds, hydrophobic interaction and pi-pi interactions playing significant role in binding of the molecules to the enzyme. Conclusion: Most of the molecules have shown good dock score and binding energy with anti-HIV receptors but Molecules 13 and 14 have potential to act as anti-tubercular and Anti HIV and hence can be further explored for dual activity.

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A visible-light-promoted oxo-sulfonylation of ynamides with sulfonic acids is reported, giving rise to a collection of functionalized alpha-sulfonylated amides in a straightforward manner. The reaction proceeds sequentially through a cascade of electrophilic addition and photoinduced sulfonyl radical-sustained skeleton rearrangement. The high atom economy, mild reaction conditions, and wide substrate scope comprised the merits of this synthetic transformation.

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alpha-Glucosidase inhibitors have extensively been exploited for the effective management of type 2 diabetes and associated complications by significantly reducing the postprandial increase in glucose and plasma insulin levels. In this endeavour, we designed and synthesized a new series of coumarinyl iminothiazolidinone hybrid compounds (6a?o) using a one-pot multi-component approach. The hybrid structures were accessed in good chemical yields. The synthesized compounds were tested for their glucosidase inhibitory efficacy using acarbose as a standard inhibitor (IC50 = 38.2 ± 0.12 muM). In-vitro analysis of the hybrid molecules identified several potential leads for the development of potent glucosidase inhibitors with IC50 values in the range of 0.09?0.92 muM with compound 6g being the most potent drug candidate (IC50 = 0.09 ± 0.001 muM). Furthermore, compound 6f was identified as the lead inhibitor against maltase-glucoamylase with comparable inhibitory efficacy to acarbose with an IC50 value of 0.07 ± 0.016 muM. Binding interactions of potent compounds with the key residues in the active site of the glucosidase enzyme were revealed by molecular docking analysis. In summary, these new structural leads based on the hybrid pharmacophores could be developed as potential inhibitors of alpha-glucosidase for treating postprandial hyperglycemia.

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Introduction: Prodrugs have been used to improve the selectivity and efficacy of cancer therapy by targeting unique abnormal markers that are overexpressed by cancer cells and are absent in normal tissues. In this context, different strategies have been exploited and new ones are being developed each year. Areas covered: In this review, an integrated view of the potential use of prodrugs in targeted cancer therapy is provided. Passive and active strategies are discussed in light of the advantages of each one and some successful examples are provided, as well as the clinical status of several prodrugs. Among them, antibody-drug conjugates (ADCs) are the most commonly used. However, several drawbacks, including limited prodrug uptake, poor pharmacokinetics, immunogenicity problems, difficulties in selective targeting and gene expression, and optimized bystander effects limit their clinical applications. Expert opinion: Despite the efforts of different companies and research groups, several drawbacks, such as the lack of relevant in vivo models, complexity of the human metabolism, and economic limitations, have hampered the development of new prodrugs for targeted cancer therapy. As a result, we believe that the combination of prodrugs with cancer nanotechnology and other newly developed approaches, such as aptamer-conjugated nanomaterials, are efficient strategies.

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Tuberculosis (TB) is a highly dreaded, infectious, chronic, airborne disease affecting more than two million people all around the world, with more than eight million cases every calendar year. TB is the second leading infectious cause of death after HIV/AIDS. Over the past few decades, numerous efforts have been undertaken to develop new anti-TB agents. The current frontline therapy for TB consists of administering three or more different drugs (usually isoniazid, rifampin, pyrazinamide, and ethambutol) over an extended period of time. But these drugs will take 6?12 months to cure TB, along with many side effects; hence, there is an urgent need to explore new anti-TB agents. Quinoxaline derivatives are a class of compounds that show a spectrum of biological properties and the interest in these compounds is exponentially growing within the field of medicinal chemistry. Quinoxaline-1,4-di-N-oxide derivatives have shown to improve the biological results and are endowed with anti-viral, anti-cancer, anti-bacterial, and anti-protozoal activities with application in many other therapeutic areas. Since quinoxaline derivatives are regarded as a new class of effective anti-TB candidates, their 1,4-di-N-oxide analogues may show promising in vitro and in vivo anti-TB activities and might be able to prevent the drug resistance to a certain extent. Therefore, the main aim of this review is to focus on important quinoxaline and quinoxaline-1,4-di-N-oxide analogues that have shown anti-TB activities, and their structure?activity relationships for designing anti-TB agents with better efficacies. The present review will be helpful in providing insights for rational designs of more active and less toxic quinoxaline-based anti-TB prodrugs.

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Fifteen new 5-benzylidene-2-(5-methylisoxazol-3-ylimino)thiazolidin-4-one derivatives (4-18) were synthesized and evaluated for their preliminary anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES) and rotarod tests. The structures of synthesized compounds were established by IR,1H NMR,13C NMR and mass spectral data. Among the compounds studied, 5-(3-fluorobenzylidene)-2-(5-methylisoxazol-3-ylimino)thiazolidin-4-one (8) was the most potent compound, with a median effective dose of 43.9 mg/kg and a high protective index (PI) of more than 11.1 after intraperitoneal administration in mice. Compound 8 showed significant oral activity against MES-induced seizures in mice, with an ED50 of 84.2 mg/kg and a PI above 11.8. These results demonstrate that compound 8 is safer than the commercially drugs.

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Transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and its negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (Keap1), control the redox and metabolic homeostasis and oxidative stress. Inhibitors of Keap1-Nrf2 interaction are promising in oxidative stress related inflammatory diseases but now hit hurdles. By utilizing thiazolidinone moiety to shield the key carboxyl pharmacophore in Keap1-Nrf2 inhibitor, a hydrogen peroxide (H2O2)-responsive prodrug pro2 was developed. The prodrug modification improved the physicochemical properties and cell membrane permeability of the parent drug. Pro2 was stable and stayed inactive under various physiological conditions, while became active by stimulation of H2O2 or inflammation derived reactive oxygen species. Moreover, pro2 exhibited proper pharmacokinetic profile suitable for oral administration and enhanced anti-inflammatory efficiency in vivo. Thus, this novel prodrug approach may not only provide an important advance in the therapy of chronic inflammatory diseases with high level of H2O2, but also offer a fresh solution to improve the drug-like and selectivity issues of Keap1-Nrf2 inhibitors.

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3-[4-1-substituted-4-piperazinyl)butyl]-4-thiazolidinone compounds which are useful as antipsychotic, analgesic, anticonvulsant and anxiolytic agents.

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Aim. Synthesis of a series of thiazolidinone-and pyrazoline-related compounds. In vitro screening of antiplasmodial activity of versatile heterocyclic derivatives. Methods: Organic wet synthesis, analytical and spectral methods, pharmacological screening, SAR analysis. Results. A series of different thiazolidinone-and pyrazoline-based derivatives was screened against Plasmodium falciparum in in vitro assays. 5-(Z)-Arylidene-2-arylidenehydrazono-3-(4-hydroxyphenyl)-4-thiazolidinones showed high growth inhibition rates with the IC50-2.32-2.39 muM. 5-Bromo-1-[2-[3-(4-chlorophenyl)-5-(4-methoxyphenyl)-3,4-dihydropyrazol-2-yl]-2-oxoethyl]indoline-2,3-dione 3 was the most active compound among tested with the IC50-1.81 muM. Based on the screening data some structure-activity relationships were derived. Conclusions. A set of different thiazolidinone-and pyrazoline-related derivatives with antitrypanosomal and anticancer properties was screened against Plasmodium falciparum. Hitcompounds inhibiting growth of the parasite at micromolar concentrations were identified. The obtained results provide further avenues to develop more potent antimalarial agents on the base of investigated classes of small drug-like molecules.

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