Design, computational studies, synthesis and biological evaluation of thiazole-based molecules as anticancer agents

Anuradha, .; Patel, Sagarkumar; Patle, Rajkumar; Parameswaran, Preethi; Jain, Alok; Shard, Amit

doi:10.1016/j.ejps.2019.04.005

Cited by 54 publications

(11 citation statements)

References 54 publications

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“…These interactions are responsible for the apoptotic action of thiazole compounds on cancer cells. The heterocycle is a pharmacophore for anticancer agents such as epothilones, ixabepilone, bleomycin, thiazofurine, dasatinib, and kud773 [ 237 ].…”

Section: Synthetic Derivatives Of Chalcones With Anticancer Propertiesmentioning

confidence: 99%

Anticancer Activity of Natural and Synthetic Chalcones

Constantinescu

Lungu²

2021

IJMS

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Cancer is a condition caused by many mechanisms (genetic, immune, oxidation, and inflammatory). Anticancer therapy aims to destroy or stop the growth of cancer cells. Resistance to treatment is theleading cause of the inefficiency of current standard therapies. Targeted therapies are the most effective due to the low number of side effects and low resistance. Among the small molecule natural compounds, flavonoids are of particular interest for theidentification of new anticancer agents. Chalcones are precursors to all flavonoids and have many biological activities. The anticancer activity of chalcones is due to the ability of these compounds to act on many targets. Natural chalcones, such as licochalcones, xanthohumol (XN), panduretin (PA), and loncocarpine, have been extensively studied and modulated. Modification of the basic structure of chalcones in order to obtain compounds with superior cytotoxic properties has been performed by modulating the aromatic residues, replacing aromatic residues with heterocycles, and obtaining hybrid molecules. A huge number of chalcone derivatives with residues such as diaryl ether, sulfonamide, and amine have been obtained, their presence being favorable for anticancer activity. Modification of the amino group in the structure of aminochalconesis always favorable for antitumor activity. This is why hybrid molecules of chalcones with different nitrogen hetercycles in the molecule have been obtained. From these, azoles (imidazole, oxazoles, tetrazoles, thiazoles, 1,2,3-triazoles, and 1,2,4-triazoles) are of particular importance for the identification of new anticancer agents.

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Section: Synthetic Derivatives Of Chalcones With Anticancer Propertiesmentioning

confidence: 99%

Anticancer Activity of Natural and Synthetic Chalcones

Constantinescu

Lungu²

2021

IJMS

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“…The vinyl ketone part of the chalcones is not only responsible for the biological activities of chalcones but is also useful as a key synthon for the preparation of different heterocyclic compounds of pharmacological interest [ 5 ]. Thiazole and chalcone derivatives possess a broad spectrum of bioactivities, including antitubercular [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ], anticancer [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], antioxidant [ 33 , 34 , 35 , 36 , 37 , 38 ], antifungal [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ] and antibacterial [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The nature of the substituents as...…”

Section: Introductionmentioning

confidence: 99%

Thiazole–Chalcone Hybrids as Prospective Antitubercular and Antiproliferative Agents: Design, Synthesis, Biological, Molecular Docking Studies and In Silico ADME Evaluation

Kasetti

Singhvi

Nagasuri³

et al. 2021

Molecules

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Compounds bearing thiazole and chalcone pharmacophores have been reported to possess excellent antitubercular and anticancer activities. In view of this, we designed, synthesized and characterized a novel series of thiazole−chalcone hybrids (1–20) and further evaluated them for antitubercular and antiproliferative activities by employing standard protocols. Among the twenty compounds, chalcones 12 and 7, containing 2,4-difluorophenyl and 2,4-dichlorophenyl groups, showed potential antitubercular activity higher than the standard pyrazinamide (MIC = 25.34 µM) with MICs of 2.43 and 4.41 µM, respectively. Chalcone 20 containing heteroaryl 2-thiazolyl moiety exhibited promising antiproliferative activity against the prostate cancer cell line (DU-145), higher than the standard methotrexate (IC50 = 11 ± 1 µM) with an IC50 value of 6.86 ± 1 µM. Furthermore, cytotoxicity studies of these compounds against normal human liver cell lines (L02) revealed that the target molecules were comparatively less selective against L02. Additional computational studies using AutoDock predicted the key binding interactions responsible for the activity and the SwissADME tool computed the in silico drug likeliness properties. The lead compounds generated through this study, create a way for the optimization and development of novel drugs against tuberculosis infections and prostate cancer.

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“…Although PKM2 occurs in normal cells, it is highly expressed in cancerous tissues. Currently, several approaches are available for drug design and we have designed the IMID-2 molecule {2- [4-(3,4-dichlorophenyl)piperazin-1-yl]-1-(imidazo[1,2-a]pyrimidin-3-yl)ethanone} using a de novo drug design approach (Anuradha et al, 2019;Schneider & Fechner, 2005). This was also possible because the structure of PKM2 is well known.…”

Section: Introductionmentioning

confidence: 99%

Metabolite profiling of IMID‐2, a novel anticancer molecule of piperazine derivative: In silico prediction, in vitro and in vivo metabolite characterization using UPLC–QTOF–MS/MS

Panday

Thakkar

Patel

et al. 2021

Biomedical Chromatography

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IMID‐2, a newly identified piperazine‐based anticancer molecule, has been shown to be cytotoxic against various cancer cell lines. The primary aim of this research was to identify and characterize possible metabolites of the molecule formed during biotransformation. A metabolite identification study was first executed using an in silico tool to predict the possible metabolism sites of IMID‐2. Thereafter, metabolites generated in vitro (rat liver microsomes, rat S9 fractions and human liver microsomes) and in vivo (rat plasma, urine and feces) were identified and characterized employing UPLC–QTOF–MS/MS. A total of eight metabolites, among which were six in phase I and two in phase II reactions, were recognized. The plausible structure of the metabolites and probable metabolic pathway have been established based on the mass fragmentation pattern, mass ppm error, ring double bond calculation and nitrogen rule. The majority of phase I metabolites were generated by N‐oxidation, hydroxylation, oxidative deamination followed by reduction, oxidative dechlorination, N‐dearylation, and N‐dealkylation. Glucuronidation played a significant role in the formation of phase II metabolites of the molecule.

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Design, computational studies, synthesis and biological evaluation of thiazole-based molecules as anticancer agents

Cited by 54 publications

References 54 publications

Anticancer Activity of Natural and Synthetic Chalcones

Anticancer Activity of Natural and Synthetic Chalcones

Thiazole–Chalcone Hybrids as Prospective Antitubercular and Antiproliferative Agents: Design, Synthesis, Biological, Molecular Docking Studies and In Silico ADME Evaluation

Metabolite profiling of IMID‐2, a novel anticancer molecule of piperazine derivative: In silico prediction, in vitro and in vivo metabolite characterization using UPLC–QTOF–MS/MS

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