Synthesis, molecular modelling and QSAR study of new N-phenylacetamide-2-oxoindole benzensulfonamide conjugates as carbonic anhydrase inhibitors with antiproliferative activity

Abstract

In continuation of our previous studies to optimise potent carbonic anhydrase inhibitors, two new series of isatin N- phenylacetamide based sulphonamides were synthesised and screened for their human (h) carbonic anhydrase (EC 4.2.1.1) inhibitory activities against four isoforms h CA I, h CA II, h CA IX and h CA XII. The indole-2,3-dione derivative 2h showed the most effective inhibition profile against h CAI and h CA II (K I = 45.10, 5.87 nM) compared to acetazolamide ( AAZ) as standard inhibitor. Moreover, 2h showed appreciable inhibition activity against the tumour-associated h CA XII, similar to AAZ showing K I of 7.91 and 5.70 nM, respectively. The analogs 3c and 3d showed good cytotoxicity effects, and 3c revealed promising selectivity towards lung cell line A549. Molecular docking was carried out for 2h and 3c to predict their binding conformations and affinities towards the h CA I, II, IX and XII isoforms.

Imidazole‐hydrazone derivatives: Synthesis, characterization, X‐ray structures and evaluation of anticancer and carbonic anhydrase I–II inhibition properties

“…In light of this, numerous hCA isoforms are regarded as desirable therapeutic targets for various pharmacological uses. [5,6] The precise physiological significance of CA I, which is widely distributed across many tissues and contributes to various pathological conditions such as retinal and brain edema, is poorly unknown. Additionally, abundant in numerous tissues, CA II is important in many disease states, including glaucoma, epilepsy, edema, high altitude condition, and kidney illness.…”

“…Fluctuations in CA expression levels can cause cancer, neuropathic pain, altitude sickness, glaucoma, epilepsy, hypertension, and more. In light of this, numerous hCA isoforms are regarded as desirable therapeutic targets for various pharmacological uses [5,6] . The precise physiological significance of CA I, which is widely distributed across many tissues and contributes to various pathological conditions such as retinal and brain edema, is poorly unknown.…”

QSAR modelling, ADMET prediction, molecular docking and molecular dynamics studies of novel 2-amino thiazole derivatives as Aurora kinase inhibitors

“…It was repeated until there were no longer any descriptors that could be removed without causing any statistically signi cant loss of t. These criteria were utilised to create three models. For future enhancement, the best prediction model with the fewest descriptors, the highest determination coe cient (R 2 ), [12][13][14], and no descriptor collinearity was chosen as shown in Table 2.…”

Synthesis of 2,3‐Disubstituted Quinoline‐4‐carbonitriles through Truce–Smiles Rearrangement of Phenacyl‐4‐nitrobenzenesulfonamides

“…2/4-Nitrobenzenesulfonamides are useful intermediates for preparing various molecular scaffolds using solid-phase [1] and solution-phase synthesis. [2,3] In the presence of the proximal CÀ H group activated by the electron-withdrawing effect, the nitrobenzenesulfonyl scaffold can undergo intramolecular nucleophilic attack, resulting in C-arylation via Truce-Smiles rearrangement. [4] Recently, intramolecular C-arylation was extensively studied for aliphatic nitrobenzenesulfonamides originating from α-amino acids.…”