N‐substituted hydroxynaphthalene imino‐oxindole derivatives as new class of <scp>PI</scp>3‐kinase inhibitor and breast cancer drug: Molecular validation and structure–activity relationship studies

Kumar, Manish; Dhayabaran, V. Violet

doi:10.1111/cbdd.13079

Cited by 18 publications

(3 citation statements)

References 31 publications

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“…The early passage of the proposed cancer cell lines used in this study was developed and cultured as previously described (please refer to the Supporting Information for detailed protocols). The anticancer activity of amide substituted ( Z )‐β‐enaminones on various cancer cell lines was determined by the MTT (3‐(4,5‐dimethylthiazol‐2yl)‐2,5‐diphenyl tetrazolium bromide) assay.…”

Section: Methodsmentioning

confidence: 99%

Pharmacological explorations of eco-friendly amide substituted (Z)-β-enaminones as anti-breast cancer drugs

Subramamiam

Ramasubbu²,

Arokiyaraj

et al. 2018

Arch. Pharm. Chem. Life Sci.

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Amide substituted (Z)-β-enaminones were synthesized by green chemistry and stereospecific synthetic pathway as novel phosphoinositide 3-kinase (PI3K) inhibitors and breast cancer drugs. PI3K inhibition was measured by competitive ELISA. A panel of cancer cell lines including MCF-7 (breast cancer), G-361 (skin cancer), and HCT 116 (colon cancer) were used to assess the anticancer potentials. In the PI3K assay, 2c and 2f were indolent for the proposed inhibitory action, which was recognized from the obtained IC 50 (>1.0 μM). Excellent activity potential of 2a, 2b, and 2d was recognized from the IC 50 range (<0.05 μM) whereas an intermediate action potential was observed for compounds 2e and 2i (IC 50 0.1 and 0.25, respectively). The docking results exclusively proposed that the hydrophobic interactions in the PI3K binding pocket were overwhelmed by the binding affinity of the most potent ligands (2a, 2b, and 2d: inhibitory constant K i = 18.16, 84.87, and 56.14 nM). MTT assay results revealed the antiproliferative activity domination of selected compounds (2a, 2b, and 2d) toward MCF-7. The relative activities of 2a, 2b, and 2d of 84.56, 80.87, and 90.12%, respectively, were comparable to that of the standard, doxorubicin (82.16%). SAR studies demonstrated amide substituted (Z)-β-enaminones as precise PI3K inhibitors to treat breast cancer. K E Y W O R D S amide substituted (Z)-β-enaminones, anticancer, breast cancer, molecular docking, phosphoinositide 3-kinase, SAR

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Section: Methodsmentioning

confidence: 99%

Pharmacological explorations of eco-friendly amide substituted (Z)-β-enaminones as anti-breast cancer drugs

Subramamiam

Ramasubbu²,

Arokiyaraj

et al. 2018

Arch. Pharm. Chem. Life Sci.

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“…Anticancer properties of substituted indoline‐based dihydroxy‐carbamides ( 5a–i ) on a panel of cell lines were resolute by MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide) assay as we described earlier . Doxorubicin was used as the standard drug in this study because it is generally used in the treatment of many types of carcinoma (solid tumors) and soft tissue sarcomas including blood cancers, like leukemia and lymphoma.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and Molecular Drug Efficacy of Indoline‐based Dihydroxy‐thiocarbamides: Inflammation Regulatory Property Unveiled over COX‐2 Inhibition, Molecular Docking, and Cytotoxicity Prospects

M¹,

Dhayabaran²

2018

Journal of Heterocyclic Chem

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in Wiley Online Library (wileyonlinelibrary.com).In this study, substituted indoline-based dihydroxy-carbamides (5a-i) were synthesized and evaluated as the cyclooxygenase-2 (COX-2) inhibitors to testify their inflammatory regulations through COX-2 inhibition. Enzyme-linked immunosorbent assay-based competitive (COX-2) inhibition (in vitro) followed by a molecular docking study (in silico) was executed to ensure the mode of interaction between 5a-i and COX-2. Apart from COX-2 inhibition studies, free-radical scavenging ability (H 2 O 2 estimation method) and the human red blood cell membrane protection (in vitro anti-inflammatory) capability of the compounds 5a-i assessment were also evaluated. Excellent antimicrobial and anticancer activity exhibited by thiocarbamide substituted compounds (5a-d) than carbamide (5e-i). In molecular docking studies, the obtained binding affinity values of 5a-i indicated the therapeutic selectivity on COX-2 (PDB ID: 1CX2) over COX-1 (PDB ID: 1EQG). Established inhibitory constant (ki) values were found as low as in nanomolar/picomolar against COX-2. Reliable COX-2 inhibition of 78-92% and IC 50 0.002-1.28 μM were obtained. Human red blood cell membrane was found to be effectively stabilized/protected by 5a-i up to 98%. Excellent antioxidant property (average radical scavenging 92%) and structure-activity relationship predictions confirmed the druggability potentials of 5a-i as effective, future anti-inflammatory drugs. The cytotoxicity of the compounds was also unveiled by MTT assay using MCF-7 (human breast cancer), SW620 (human colon cancer), G361 (human skin cancer), human breast normal cell lines (MCF-10), and cell lines.

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“…The search for a new pharmacotherapy from medicinal plants to treat cancers has considerably progressive. A wide range of researchers who keenly discover synthetic medicines to treat breast cancer [1][2][3][4][5][6]. But still, the safety is questioned.…”

Section: Introductionmentioning

confidence: 99%

Exploration of anti-breast cancer effects of Terminalia chebula extract on DMBA-induced mammary carcinoma in Sprague Dawley rats

Henry¹,

Ranjan²,

Murugan³

et al. 2020

Futur J Pharm Sci

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Background Plant extracts are effectively acting as the natural medicinal cocktail, non-side effective, efficacious, and freely available. The present study aimed to unveil the pharmacological and medicinal effects of Terminalia chebula plant extract in 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinoma in Sprague Dawley rats. The plant extract obtained was subjected to in vivo antioxidant and anticancer studies in various concentrations after an analytical technique such as FTIR, GCMS, and HPLC-based chemo-profiling in Sprague Dawley rats. Results Apart from the antiproliferative effect on breast cancer cell line (MCF-7) and normal breast epithelial cells (MCF-10a), we have measured the changes in body weight, along with other tumor parameters such as tumor volume, tumor incidence, tumor weight, tumor burden, serum biochemical parameters, and histopathological findings of breast tissue. As the oxidative stress further enhances the development of cancer, the antioxidant property of the plant extract demonstrates its use against cancer treatment. One hundred fifty milligrams per milliliter (IC50 250 μg/mL) concentration of the ethanolic extract was vital for the proliferation of MCF-7 cell lines (Fig. 7a). Meanwhile, 300 μg/mL (IC50 150 μg/mL) was an effective dose to attain a maximum HDAC inhibition of 78%. Also, the normal liver and kidney functioning revealed the non-toxicity nature of the plant. Conclusion Terminalia chebula could be one of the effective naturally obtained anti-breast cancer medications. Isolation and characterization of individual bioactive compounds of T. chebula would be the future perspective.

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N‐substituted hydroxynaphthalene imino‐oxindole derivatives as new class of PI3‐kinase inhibitor and breast cancer drug: Molecular validation and structure–activity relationship studies

Cited by 18 publications

References 31 publications

Pharmacological explorations of eco-friendly amide substituted (Z)-β-enaminones as anti-breast cancer drugs

Pharmacological explorations of eco-friendly amide substituted (Z)-β-enaminones as anti-breast cancer drugs

Synthesis and Molecular Drug Efficacy of Indoline‐based Dihydroxy‐thiocarbamides: Inflammation Regulatory Property Unveiled over COX‐2 Inhibition, Molecular Docking, and Cytotoxicity Prospects

Exploration of anti-breast cancer effects of Terminalia chebula extract on DMBA-induced mammary carcinoma in Sprague Dawley rats

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