Caspase‐3: A primary target for natural and synthetic compounds for cancer therapy

Chemical Biology & Drug Design, Год журнала: 2021, Номер 98(1), С. 144 - 165

Опубликована: Май 9, 2021

Caspases, a group of protease enzymes (cysteine proteases), exist as inactive zymogens in the cells and execute apoptosis (programmed cell death). Caspase-3, an executioner caspase, plays imperative role becomes primary target for cancer treatment. A number analogues quinazoline, quinazolinone, indoloquinazolines, quinone, naphthoquinones, pyrroloiminoquinones, styrylquinolines, tetheredtetrahydroquinoline, fluoroquinolone, thiosemicarbazones, benzotriazole, pyrimidines, chalcone, carbazoles have been reported till date, representing caspase-3 mediated therapy. Simultaneously, plant isolates, including lysicamine, podophyllotoxin, majoranolide, also claimed caspase-3-mediated apoptosis-induced cytotoxicity. Procaspase-activating compound-1 (PAC-1) is first FDA approved orphan drug, its synthetic derivative WF-208 showed fascinating anticancer activity. Till large compounds patented their cytotoxicity now scientist focusing to introduce new market encompass

Язык: Английский

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Discovery of new pyrimidine-5-carbonitrile derivatives as anticancer agents targeting EGFR^WTand EGFR^T790M

Organic & Biomolecular Chemistry, Год журнала: 2020, Номер 18(38), С. 7608 - 7634

Опубликована: Янв. 1, 2020

A new series of pyrimidine-5-carbonitrile derivatives has been designed as ATP mimicking tyrosine kinase inhibitors the epidermal growth factor receptor (EGFR).

Язык: Английский

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Design, synthesis, and biological evaluation of new challenging thalidomide analogs as potential anticancer immunomodulatory agents

Bioorganic Chemistry, Год журнала: 2020, Номер 104, С. 104218 - 104218

Опубликована: Сен. 1, 2020

Язык: Английский

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Antitumor properties of certain spirooxindoles towards hepatocellular carcinoma endowed with antioxidant activity

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2020, Номер 35(1), С. 831 - 839

Опубликована: Янв. 1, 2020

In the current medical era, spirooxindole motif stands out as a privileged heterospirocyclic scaffold that represents core for wide range of bioactive naturally isolated products (such Strychnofoline and spirotryprostatins A B) synthetic compounds. Interestingly, no much attention has been paid to develop derivatives with dual antioxidant anticancer activities. this context, series spirooxindoles 6a-p was examined their effect towards HepG2 hepatocellular carcinoma PC-3 prostate cancer cell lines. Spirooxindole 6a found be an efficient anti-proliferative agent both cells (IC50 = 6.9 11.8 µM, respectively). Afterwards, assessed its apoptosis induction potential in cells, where pro-apoptotic impact approved via significant elevation Bax/Bcl-2 ratio expression levels caspase-3,

Язык: Английский

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New quinoxaline derivatives as VEGFR-2 inhibitors with anticancer and apoptotic activity: Design, molecular modeling, and synthesis

Bioorganic Chemistry, Год журнала: 2021, Номер 110, С. 104807 - 104807

Опубликована: Март 6, 2021

Язык: Английский

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3-Hydrazinoisatin-based benzenesulfonamides as novel carbonic anhydrase inhibitors endowed with anticancer activity: Synthesis, in vitro biological evaluation and in silico insights

European Journal of Medicinal Chemistry, Год журнала: 2019, Номер 184, С. 111768 - 111768

Опубликована: Окт. 8, 2019

Язык: Английский

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Design, molecular docking, in vitro, and in vivo studies of new quinazolin-4(3H)-ones as VEGFR-2 inhibitors with potential activity against hepatocellular carcinoma

Bioorganic Chemistry, Год журнала: 2020, Номер 107, С. 104532 - 104532

Опубликована: Дек. 8, 2020

Язык: Английский

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New bis([1,2,4]triazolo)[4,3-a:3′,4′-c]quinoxaline derivatives as VEGFR-2 inhibitors and apoptosis inducers: Design, synthesis, in silico studies, and anticancer evaluation

Bioorganic Chemistry, Год журнала: 2021, Номер 112, С. 104949 - 104949

Опубликована: Апрель 30, 2021

Язык: Английский

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Development of isatin-thiazolo[3,2-a]benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological and molecular dynamics investigations

Bioorganic Chemistry, Год журнала: 2021, Номер 110, С. 104748 - 104748

Опубликована: Фев. 18, 2021

Язык: Английский

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Discovery of new quinolines as potent colchicine binding site inhibitors: design, synthesis, docking studies, and anti-proliferative evaluation

Journal of Enzyme Inhibition and Medicinal Chemistry, Год журнала: 2021, Номер 36(1), С. 640 - 658

Опубликована: Янв. 1, 2021

Discovering of new anticancer agents with potential activity against tubulin polymerisation is still a promising approach. Colchicine binding site inhibitors are the most relevant anti-tubulin agents. Thus, quinoline derivatives have been designed and synthesised to possess same essential pharmacophoric features colchicine inhibitors. The compounds were tested in vitro panel three human cancer cell lines (HepG-2, HCT-116, MCF-7) using as positive control. Comparing (IC50 = 7.40, 9.32, 10.41 µM HepG-2, MCF-7, respectively), 20, 21, 22, 23, 24, 25, 26, 28 exhibited superior cytotoxic activities IC50 values ranging from 1.78 9.19 µM. In order sightsee proposed mechanism anti-proliferative activity, active members further evaluated for their inhibitory polymerisation. Compounds 21 32 highest effect 9.11 10.5 nM, respectively. Such showed higher than that 10.6 nM) CA-4 13.2 nM). impact compound 25 on cycle distribution was assessed. results revealed can arrest at G2/M phase. Annexin V PI double staining assay carried out explore apoptotic compounds. Compound induced HepG-2 thirteen times more control cells. To examine pattern target heterodimers site, molecular docking studies out.

Язык: Английский

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