Indoline-5-Sulfonamides: A Role of the Core in Inhibition of Cancer-Related Carbonic Anhydrases, Antiproliferative Activity and Circumventing of Multidrug Resistance

doi:10.3390/ph15121453

Paper

Indoline-5-Sulfonamides: A Role of the Core in Inhibition of Cancer-Related Carbonic Anhydrases, Antiproliferative Activity and Circumventing of Multidrug Resistance

Published Nov 23, 2022 · S. Krymov, A. Scherbakov, L. Dezhenkova

Pharmaceuticals

Q1 SJR score

9

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0

Influential Citations

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Abstract

The overexpression and activity of carbonic anhydrase (CA, EC 4.2.1.1) isoforms CA IX and CA XII promote the accumulation of exceeding protons and acidosis in the extracellular tumor environment. Sulfonamides are effective inhibitors of most families of CAs. In this study, using scaffold-hopping, indoline-5-sulfonamide analogs 4a–u of the CA IX-selective inhibitor 3 were designed and synthesized to evaluate their biological properties. 1-Acylated indoline-5-sulfonamides demonstrated inhibitory activity against tumor-associated CA IX and XII with KI values up to 132.8 nM and 41.3 nM. Compound 4f, as one of the most potent inhibitors of CA IX and XII, exhibits hypoxic selectivity, suppressing the growth of MCF7 cells at 12.9 µM, and causes partial inhibition of hypoxia-induced CA IX expression in A431 skin cancer cells. 4e and 4f reverse chemoresistance to doxorubicin of K562/4 with overexpression of P-gp.

In Vitro Study

Study Snapshot

Indoline-5-sulfonamides show inhibitory activity against cancer-associated carbonic anhydrases, antiproliferative activity, and can circumvent multidrug resistance in cancer cells.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Indoline-5-Sulfonamides: A Role of the Core in Inhibition of Cancer-Related Carbonic Anhydrases, Antiproliferative Activity and Circumventing of Multidrug Resistance

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References

Citations

Synthesis and evaluation of sulfonamide derivatives of quinoxaline 1,4-dioxides as carbonic anhydrase inhibitors

Sulfonamide-derived quinoxaline 1,4-dioxides show promising inhibitory activity against carbonic anhydrases, with potential for developing chemotherapeutic agents targeting carbonic anhydrases.

Cellular Pre-Adaptation to the High O2 Concentration Used in Standard Cell Culture Confers Resistance to Subsequent H2O2-Induced Cell Death

Pre-adapting squamous cell carcinoma cells to standard cell culture oxygenation of 18.6% O2 resists H2O2-induced cell death, potentially due to increased activation of Nrf-2.

Synthesis of some Sulfonamide Derivatives coupled with Salicylamide or Anisamide Scaffold as Potent PD-L1 Inhibitors and their Anti-proliferation Assay

Sulfonamide derivatives coupled with salicylamide or anisamide scaffold show promising results as PD-L1 inhibitors, with compound 31 showing remarkable anti-proliferative activity against MCF-7, DU-145, and PC-3 human prostate cancer cell lines.

Targeting carbonic anhydrases for the management of hypoxic metastatic tumors

Targeting carbonic anhydrases with selective inhibitors may lead to a breakthrough in treating hypoxic metastatic tumors.