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In silico identification of 2-oxo-1,3-thiazolidine derivatives as novel inhibitor candidate of class II histone deacetylase (HDAC) in cervical cancer treatment

Cervical cancer ranks third among the most prevalent deadly cancer in women worldwide and ranks first in developing countries. It is caused by human papilloma virus (HPV) infection. Thus HDACs have become prominent inhibition target for cervical cancer treatment. In order to discover the new alternative HDAC inhibitors (HDACIs), we conducted a computer-aided drug discovery and development (CADDD) based on de novo approach. The compound library is based on 4-[(2-oxo-1,3-thiazolidin-3-yl)carbonyl] aniline. Screening of the best drug leads was evaluated from several parameters, such as docking and interaction analysis, pharmacology, in silico preclinical trial and molecular dynamics analysis. The inhibitory activity of these new designed ligands against Homo sapiens class II HDAC was determined by molecular docking simulation. Docking analysis yielded eight best ligands which have better binding affinity than the standards. Therefore, interaction analysis indicated that all best ligands performed coordination with Zn2+ cofactor in HDAC charge-relay system which are essential for HDAC inhibitory activities of these inhibitors. Pharmacology analysis and preclinical trials of these compounds including pharmacology properties, bioactivity, mutagenicity?carcinogenicity, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties were done through in silico methods. Through this analysis, the best ligands meet Lipinski’s rule of five, have a better drug score than standards, and show good bioactivities, oral bioavailability and ADMET properties. All best ligands also have good synthetic accessibility and were proved to be new compounds that have never been synthesized before. Stability of HDAC?ligand complexes was also calculated through molecular dynamics (MD) simulation. Based on this simulation, complex of the best ligands with corresponding HDAC has a good stability based on RMSD (root mean square deviation) and interaction analysis. The study thus reveals eight best ligands (F, Ib14, O38, Kb17, Gd40, Aa50, Gc42 and Bb38) which have better binding affinity against human class II histone deacetylase (HDAC) through molecular docking, dynamics and interaction analysis. The best ligands were also found to have good bioactivities, oral bioavailability and ADMET properties through in silico pharmacology analysis and preclinical trial. These compounds were found to have a good synthetic accessibility; therefore they could be synthesized for further biological and clinical test.

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Synthetic 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones exhibit selective in?vitro antitumoral activity and inhibit cancer cell growth in a preclinical model of glioblastoma multiforme

Glioblastoma multiforme (GBM) is the worst form of primary brain tumor, which has a high rate of infiltration and resistance to radiation and chemotherapy, resulting in poor prognosis for patients. Recent studies show that thiazolidinones have a wide range of pharmacological properties including antimicrobial, anti-inflammatory, anti-oxidant and anti-tumor. Here, we investigate the effect antiglioma in?vitro of a panel of sixteen synthetic 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones where 13 of these decreased the viability of glioma cells 30?65% (100?muM) compared with controls. The most promising compounds such as 4d, 4l, 4m and 4p promoted glioma reduction of viability greater than 50%, were further tested at lower concentrations (12.5, 25, 50 and 100?muM). Also, the data showed that the compounds 4d, 4l, 4m and 4p induced cell death primarily through necrosis and late apoptosis mechanisms. Interestingly, none of these 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones were cytotoxic for primary astrocytes, which were used as a non-transformed cell model, indicating selectivity. Our results also show that the treatment with sub-therapeutic doses of 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones (4d, 4l and 4p) reduced in?vivo glioma growth as well as malignant characteristics of implanted tumors such as intratumoral hemorrhage and peripheral pseudopalisading. Importantly, 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones treatment did not induce mortality or peripheral damage to animals. Finally, 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones also changed the nitric oxide metabolism which may be associated with reduced growth and malignity characteristics of gliomas. These data indicates for the first time the therapeutic potential of synthetic 2-aryl-3-((piperidin-1-yl)ethyl)thiazolidin-4-ones to GBM treatment.

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Saturated Five-Membered Thiazolidines and Their Derivatives: From Synthesis to Biological Applications

In past decades, interdisciplinary research has been of great interest for scholars. Thiazolidine motifs behave as a bridge between organic synthesis and medicinal chemistry and compel researchers to explore new drug candidates. Thiazolidine motifs are very intriguing heterocyclic five-membered moieties present in diverse natural and bioactive compounds having sulfur at the first position and nitrogen at the third position. The presence of sulfur enhances their pharmacological properties, and, therefore, they are used as vehicles in the synthesis of valuable organic combinations. They show varied biological properties viz. anticancer, anticonvulsant, antimicrobial, anti-inflammatory, neuroprotective, antioxidant activity and so on. This diversity in the biological response makes it a highly prized moiety. Based on literature studies, various synthetic approaches like multicomponent reaction, click reaction, nano-catalysis and green chemistry have been employed to improve their selectivity, purity, product yield and pharmacokinetic activity. In this review article, we have summarized systematic approaches for the synthesis of thiazolidine and its derivatives, along with their pharmacological activity, including advantages of green synthesis, atom economy, cleaner reaction profile and catalyst recovery which will help scientists to probe and stimulate the study of these scaffolds.

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Electric Literature of 5908-62-3, The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.5908-62-3, Name is 1,1-Dioxo-isothiazolidine, molecular formula is C3H7NO2S. In a Article£¬once mentioned of 5908-62-3

N-Nitroso Sultams: On the Direction of Approach of Nucleophiles to the Sulfonyl Group

The N-nitroso derivatives of propanesultam, butanesultam, and pentanesultam were synthesized along with N-nitropropanesultam and N-nitro-N-methylmethanesulfonamide.The decompositions of the N-nitroso sultams, wich increase in rate with increasing ring size, yield the corresponding sultones and also varying amounts of regenerated sultams.These reactions are discussed in terms of higher energy pathway involving approach of the nucleophile in a direction between of sulfonyl oxygens (on the O, O, N face) and a lower energy pathway involving the conformer which permits approach of the nucleophile trans to and colinear with one of the coordinate covalent oxygen atoms (on R, O, N face). The mechanisms of the decomposition of the N-nitro sulfonamides and the tosyloxy diimide N-oxides are also discussed.N-nitrosopropanesultam (and the butyl analoque) are potent inhibitors of proteinase alpha-chymotrypsin.

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Related Products of 2682-49-7, Chemistry is the science of change. But why do chemical reactions take place? Why do chemicals react with each other? The answer is in thermodynamics and kinetics.In a document type is Review, and a compound is mentioned, 2682-49-7, Thiazolidin-2-one, introducing its new discovery.

Roles of pyridine and pyrimidine derivatives as privileged scaffolds in anticancer agents

Background: Cancer has been considered to be a global health concern due to the impact of disease on the quality of life. The continual increase of cancer cases as well as the resistance of cancer cells to the existing drugs have driven the search for novel anticancer drugs with better potency and selectivity, improved pharmacokinetic profiles, and minimum toxicities. Pyridine and pyrimidine are presented in natural products and genetic materials. These pyridine/pyrimidine core structures have been noted for their roles in many biological processes as well as in cancer pathogenesis, which make such compounds become attractive scaffolds for discovery of novel drugs. Results & Conclusion: In the recent years, pyridine- and pyrimidine-based anticancer drugs have been developed based on structural modification of these core structures (i.e., substitution with moieties and rings, conjugation with other compounds, and coordination with metal ions). Detailed discussion is provided in this review to highlight the potential of these small molecules as privileged scaffolds with attractive properties and biological activities for the search of novel anticancer agents.

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2682-49-7, Name is Thiazolidin-2-one, belongs to thiazolidine compound, is a common compound. SDS of cas: 2682-49-7In an article, once mentioned the new application about 2682-49-7.

New prospects for the development of selective inhibitors of alpha-glucosidase based on coumarin-iminothiazolidinone hybrids: Synthesis, in-vitro biological screening and molecular docking analysis

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 ¡À 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 ¡À 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 ¡À 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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Application of 2682-49-7, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 2682-49-7, molcular formula is C3H5NOS, introducing its new discovery.

Molecules with versatile biological activities bearing antipyrinyl nucleus as pharmacophore

Antipyrine (1,2-dihydro-1,5-dimethyl-2-phenylpyrazole-3-one) in a structural frame consists of a five membered lactam pyrazolone heterocyclic ring as a pharmacophore moiety. It is evident from literature that the molecules having nitrogen bearing heterocyclic nuclei clearly exhibit several biological actions. Commercially available pyrazolone derivatives as drugs, analgin and metamizol are an established chemical class of analgesics. Recent trends of synthetic routes and several biological actions of antipyrine analogues are considered in this review. Indeed, the synthesized derivatives possess antipyrine moiety having versatile biological properties, antimicrobial, antitubercular, anthelmintic, antioxidant, analgesic, anti-inflammatory, cytotoxic and antiviral activities.

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Quinuclidine | C7H437N | ChemSpider

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Synthesis and biological evaluation of 4-thiazolidinone derivatives as antitubercular and antimicrobial agents

New series of N-[2-{2-(substitutedphenyl)-4-oxo-5-(substitutedbenzylidene)-1,3-thiazolidine}-iminoethyl]-2-amino-5-nitrothiazole, 5(a-m) have been synthesized from 2-amino-5-nitrothiazole as a starting material by conventional as well as microwave methods. All the synthesized compounds 4(a-m) were screened for their antibacterial and antifungal activities against some selected bacteria and fungi and antitubercular activity screened against Mycobacterium tuberculosis. The structure of all the synthesized compounds were confirmed by chemical and spectral analyses such as IR, 1H NMR, 13C NMR and FAB-Mass.

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Reference of 2682-49-7, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In a article, 2682-49-7, molcular formula is C3H5NOS, introducing its new discovery.

Synthesis of some 5-(substituted benzylidene)-3-phenyl-2-phenylimino-1,3-thiazolidin-4-ones under ultrasound irradiation

Recently, we have synthesized environmental benign one pot synthesis of 5-(Substituted Benzylidene)-3-Phenyl-2-Phenylimino-1,3-Thiazolidin-4-Ones (a-f) under Ultrasound irradiation by cyclization of 1,3 -diphenylthiourea with a-halo acids in presence of sodium acetate in absolute ethanol for 10-15 minute. The crude compound was purified by silica gel column chromatography using n-hexane and ethyl acetate as solvent system and recrystalised from ethanol. The synthesized compounds have been screened in vitro for their antimicrobial activity against S. aureus and E.coli as compare with standard drug Streptomycin. Some of the compounds displayed pronounced biological activity. The resulting products were characterized by IR,1H NMR and13 C NMR spectroscopic method.

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Reference of 2682-49-7, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.2682-49-7, Name is Thiazolidin-2-one, molecular formula is C3H5NOS. In a article£¬once mentioned of 2682-49-7

Design, Synthesis and molecular docking study of hybrids of quinazolin-4(3H)-one as anticancer agents

A series of 4-(2-(4-substituted phenyl)-4-oxoquinazolin-3(4H)-yl)-N-(2-(4-fluorophenyl)-4-oxo-5-(arylidene)thiazolidin-3-yl) benzamides (VIa-n) have been synthesized by condensation of N-(2-(4fluorophenyl)-4-oxothiazolidin-3-yl)-4-(4-oxo-2-(4-substituted phenyl)quinazolin-3(4H)-yl)benzamides (Va-b) with various aryl/heteroaryl aldehydes using conventional methodology. All compounds were screened for their in vitro anticancer activity against the human breast cancer cell lines (MCF-7), human lung cancer cell lines (A549) using MTT assay method and doxorubicin is used as standard drug. Compound VId, VIk and VIn showed high potency against A549 cell lines with IC50 values 0.035¡À0.002 muM, 0.031¡À0.002 muM and 0.030¡À0.002 muM respectively compared to 0.023¡À0.002 muM showed by the standard. However, highest activity against MCF-7 cell lines was exhibited by Va, Vb, VIk and VIn with IC50 values between 0.040 – 0.050 muM. All the remaining compounds showed moderate anticancer activity against both the MCF-7 and A549 cell lines. To understand the interactions with active binding site of receptor, molecular docking study was also performed.

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Quinuclidine | C7H394N | ChemSpider