Synthesis and Biological Evaluation of N-(1H-Indol-6ylmethyl)benzenesulfonamide Analogs as Metabolic Inhibitors of Mitochondrial ATP Production in Pancreatic Cancer Cells (original) (raw)
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Molecular diversity, 2013
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Synthesis and Anticancer Evaluation of Benzenesulfonamide Derivatives
Heterocycles - Synthesis and Biological Activities [Working Title]
A highly efficient protocol was developed for the synthesis of 3-(indoline-1carbonyl)-N-(substituted) benzene sulfonamide analogs with excellent yields. The new 3-(indoline-1-carbonyl)-N-(substituted) benzene sulfonamide derivatives (4a-g and 5a-g) were evaluated in vitro anticancer activity against a series of different cell lines like A549 (lung cancer cell), HeLa (cervical), MCF-7 (breast cancer cell) and Du-145 (prostate cancer cell) respectively. The results of the anticancer activity data revealed that most of the tested compounds showed IC 50 values from 1.98 to 9.12 μM in different cell lines. Compounds 4b, 4d, 5d, and 5g were the most potent, with IC 50 values ranging from 1.98 to 2.72 μM in different cell lines.
Arabian Journal of Chemistry, 2014
A series of 4-(1-aryl-5-chloro-2-oxo-1,2-dihydro-indol-3-ylideneamino)-N-substituted benzenesulfonamide derivatives (1-20) was synthesized and evaluated for its in vitro antimicrobial and anticancer activities. Antimicrobial results indicated that compounds N-(4-(1-benzoyl-5-chloro-2-oxoindolin-3-ylideneamino) phenylsulfonyl)-4-isopropoxy benzamide (9) and N-(4-(5-chloro-1-(2-chlorobenzoyl)-2-oxoindolin-3-ylideneamino) phenylsulfonyl)-4-isopropoxybenzamide (19) were found to be the most effective ones. The anticancer results indicated that almost all the synthesized compounds were more active than the standard drug carboplatin but less active than the standard drug 5-fluorouracil (5-FU) against both the cell lines (HCT116 and RAW 264.7). 4-(1-Benzoyl-5-* Corresponding author. Tel.: +91 1262 393222; fax: +91 1262 274133.
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Non-invasive imaging of cyclooxygenase-2 (COX-2) by radiolabeled ligands is attractive for the diagnosis of cancer, and novel highly affine leads with optimized pharmacokinetic profile are of great interest for future developments. Recent findings have shown that methylsulfonyl-substituted (dihydro)pyrrolo[3,2,1-hi]indoles represent highly potent and selective COX-2 inhibitors but possess unsuitable pharmacokinetic properties for radiotracer applications. Based on these results, we herein present the development and evaluation of a second series of sulfonamide-substituted (dihydro)pyrrolo[3,2,1-hi]indoles and their conversion into the respective more hydrophilic N-propionamide-substituted analogs. In comparison to the methylsulfonyl-substituted leads, COX inhibition potency and selectivity was retained in the sulfonamide-substituted compounds; however, the high lipophilicity might hinder their future use. The N-propionamide-substituted analogs showed a significantly decreased lipoph...
Synthesis and Anticancer Evaluation of New Benzenesulfonamide Derivatives
European Chemical Bulletin
A highly efficient protocol was developed for the synthesis of 3-(indoline-1-carbonyl)-N-(substituted)benzenesulfonamide compounds with excellent yields. The in vitro anticancer activity of the new 3-(indoline-1-carbonyl)-N-(substituted)benzenesulfonamide derivatives against A549 (lung cancer cell), HeLa (cervical), MCF-7 (breast cancer cell) and Du-145 (prostate cancer cell) cell lines were studied. Most of the tested compounds showed anticancer activity (IC50 values ranged between 1.98 and 9.12 µM against different cell lines).
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A series of naturally occurring compounds reported recently by multiple laboratories defines a new small-molecule class sharing a unique benzolactone enamide core structure and diverse biological actions, including inhibition of growth of tumor cells and oncogene-transformed cell lines. Here we show that representative members of this class, including salicylihalamide A, lobatamides A-F, and oximidines I and II inhibit mammalian vacuolar-type (H ϩ )-ATPases (V-ATPases) with unprecedented selectivity. Data derived from the NCI 60-cell antitumor screen critically predicted the V-ATPase molecular target, while specific biochemical assays provided confirmation and further illumination. The compounds potently blocked representative V-ATPases from human kidney, liver, and osteoclastic giant-cell tumor of bone but were essentially inactive against V-ATPases of Neurospora crassa and Saccharomyces cerevisiae and other membrane ATPases. Essential regulation of pH in cytoplasmic, intraorganellar, and local extracellular spaces is provided by
International Journal of Molecular Sciences
A series of novel 2-alkythio-4-chloro-N-[imino-(heteroaryl)methyl]benzenesulfonamide derivatives, 8–24, were synthesized in the reaction of the N-(benzenesulfonyl)cyanamide potassium salts 1–7 with the appropriate mercaptoheterocycles. All the synthesized compounds were evaluated for their anticancer activity in HeLa, HCT-116 and MCF-7 cell lines. The most promising compounds, 11–13, molecular hybrids containing benzenesulfonamide and imidazole moieties, selectively showed a high cytotoxic effect in HeLa cancer cells (IC50: 6–7 μM) and exhibited about three times less cytotoxicity against the non-tumor cell line HaCaT cells (IC50: 18–20 μM). It was found that the anti-proliferative effects of 11, 12 and 13 were associated with their ability to induce apoptosis in HeLa cells. The compounds increased the early apoptotic population of cells, elevated the percentage of cells in the sub-G1 phase of the cell cycle and induced apoptosis through caspase activation in HeLa cells. For the mos...
Synthesis and identification of heteroaromatic N-benzyl sulfonamides as potential anticancer agents, 2019
Sulfonamides are a crucial class of bioisosteres that are prevalent in a wide range of pharmaceuticals, however, the available methods for their production directly from heteroaryl aldehyde reagents remains surprisingly limited. A new approach for regioselective incorporation of a sulfonamide unit to heteroarene scaffolds has been developed and is reported within. As a result, a variety of primary benzylic N-alkylsulfonamides have been prepared via a two-step (one pot) formation from the in situ reduction of an intermediate N-sulfonyl imine under mild, practical conditions. The compounds have been screened against a variety of cell lines for cytotoxicity effects using a Cell Titer Blue assay. The cell viability investigation identifies a subset of N-benzylic sulfonamides derived from the indole scaffold to be targeted for further development into novel molecules with potential therapeutic value. The most cytotoxic of the compounds prepared, AAL-030, exhibited higher potency than other well-known anticancer agents Indisulam and ABT-751.