Synthesis, anti-proliferative and genotoxicity studies of 6-chloro-5-(2-substituted-ethyl)-1,3-dihydro-2H-indol-2-ones and 6-chloro-5-(2-chloroethyl)-3-(alkyl/ary-2-ylidene)indolin-2-ones

Meti, Gangadhar Y.; Kamble, Atulkumar A.; Kamble, Ravindra R.; Somagond, Shilpa M.; Devarajegowda, H. C.; Kumari, Sandhya; Kalthur, Guruprasad; Adiga, Satish Kumar

doi:10.1016/j.ejmech.2016.05.028

Cited by 3 publications

(2 citation statements)

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“…Dose response parameters were calculated for each individual cell line, including GI 50 , TGI, and LC 50 . 68 …”

Section: Experimental Sectionmentioning

confidence: 99%

“…The experimental details of the assay and the measured activity pattern across all cancer subpanels have been reported. , Anticancer activities for the two compounds in the five-dose screen were interpreted using GI 50 (the compound’s molar concentration at which 50% net cell proliferation is inhibited), TGI (the total growth inhibition that represents the cytostatic activity), and LC 50 (cytotoxic activity which counts 50% net cell death) calculations. Dose response parameters were calculated for each individual cell line, including GI 50 , TGI, and LC 50 …”

Section: Experimental Sectionmentioning

confidence: 99%

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Discovery and Anticancer Activity of Novel 1,3,4-Thiadiazole- and Aziridine-Based Indolin-2-ones via In Silico Design Followed by Supramolecular Green Synthesis

et al. 2022

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Three crucial anticancer scaffolds, namely indolin-2-one, 1,3,4-thiadiazole, and aziridine, are explored to synthesize virtually screened target molecules based on the c-KIT kinase protein. The stem cell factor receptor c-KIT was selected as target because most U.S. FDA-approved receptor tyrosine kinase inhibitors bearing the indolin-2-one scaffold profoundly inhibit c-KIT. Molecular hybrids of indolin-2-one with 1,3,4-thiadiazole ( IIIa – m ) and aziridine ( VIa and VIc ) were afforded through a modified Schiff base green synthesis using β-cyclodextrin-SO 3 H in water as a recyclable proton-donor catalyst. A computational study found that indolin-2,3-dione forms a supramolecular inclusion complex with β-cyclodextrin-SO 3 H through noncovalent interactions. A molecular docking study of all the synthesized compounds was executed on the c-KIT kinase domain, and most compounds displayed binding affinities similar to that of Sunitinib. On the basis of the pharmacokinetic significance of the aryl thioether linkage in small molecules, 1,3,4-thiadiazole hybrids ( IIIa – m ) were extended to a new series of 3-((5-(phenylthio)-1,3,4-thiadiazol-2-yl)imino)indolin-2-ones ( IVa – m ) via thioetherification using bis(triphenylphosphine)palladium(II)dichloride as the catalyst for C–S bond formation. Target compounds were tested against NCI-60 human cancer cell lines for a single-dose concentration. Among all three series of indolin-2-ones, the majority of compounds demonstrated broad-spectrum activity toward various cancer cell lines. Compounds IVc and VIc were further evaluated for a five-dose anticancer study. Compound IVc showed a potent activity of IC 50 = 1.47 μM against a panel of breast cancer cell lines, whereas compound VIc exhibited the highest inhibition for a panel of colon cancer cell lines at IC 50 = 1.40 μM. In silico ADME property descriptors of all the target molecules are in an acceptable range. Machine learning algorithms were used to examine the metabolites and phase I and II regioselectivities of compounds IVc and VIc , and the results suggested that these two compounds could be potential leads for the treatment of cancer.

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“…Dose response parameters were calculated for each individual cell line, including GI 50 , TGI, and LC 50 . 68 …”

Section: Experimental Sectionmentioning

confidence: 99%