Design, synthesis and biological evaluation of<i>N</i>-(5-methyl-isoxazol-3-yl/1,3,4-thiadiazol-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamides as human carbonic anhydrase isoenzymes I, II, VII and XII inhibitors

Mishra, Chandra Bhushan; Kumari, Shikha; Angeli, Andrea; Monti, Simona Maria; Buonanno, Martina; Prakash, Amresh; Tiwari, Manisha

doi:10.1080/14756366.2016.1197221

Cited by 26 publications

(19 citation statements)

References 53 publications

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“…The reaction of p ‐tolyl isocyanate 9 with compounds 2 , 3 and 7 to give the corresponding urea derivatives 16 , 17 and 18 respectively, in excellent yields (94 – 96%). It is worth to mention that, Mishra et al prepared the urea derivative 17 by the reaction of the p ‐tolylisocyanate and 4‐amino‐ N ‐(5‐methylisoxazol‐3‐yl)benzenesulfonamide in DMF at reflux for 5–6 hours. Also, the compound 18 has been prepared in different methods as described in the literatures .…”

Section: Resultsmentioning

confidence: 99%

Facile Synthesis, Structural Activity Relationship, Molecular Modeling and In Vitro Biological Evaluation of New Urea Derivatives with Incorporated Isoxazole and Thiazole Moieties as Anticancer Agents

2019

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A new series of isoxazolyl and thiazolyl urea derivatives was synthesized, fully characterized and evaluated in vitro as anticancer agents. The chemistry involves a facile protocol for the preparation of urea derivatives 12–22 through the reaction of isocyanates (p‐tolylsulfonyl isocyanate, p‐tolyl isocyanate, benzoyl isocyanate and ethylisocyanate) 8–11 with the corresponding aminoisoxazoles and aminothiazoles 2, 3, 6 and 7. The cytotoxicity of the synthesized compounds 12–22 were evaluated using human lung adenocarcinoma cell line (A549), cervical cancer cell line (HeLa), and breast cancer cell line (MCF7). All novel compounds (except compounds 12, 17, and 18) were potential cytotoxic against lung cancer as it displayed IC50s less than the reference drug (5‐Fluro uracil (5FU)). All tested compounds (except 15 and 19) showed strong inhibition of breast cancer cell line even much better than the 5FU. The tested compounds were less cytotoxic against cervical cancer except compounds 16, 19, 20, and 21. The molecular docking studies of the synthesized compounds against the three different proteins Janus kinase 2 (JAK2), cyclin dependent kinase‐2 (CDK2), and B‐cell lymphoma‐2 (BCL2) that are major proteins involved in pathogenesis of cancer were discussed. The molecular‐docking analyses revealed that compounds 13, 14 and 20 were the best docked ligand compared to reference docked ligands against the tested targeted proteins. In conclusion, the urea derivatives 13 and 14 were the most promising compounds with lowest IC50s against the tested cancer cell lines, and they displayed the lowest binding energies, critical hydrogen bonds and hydrophobic interactions with the molecular targets compared to other tested compounds.

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Section: Resultsmentioning

confidence: 99%

Facile Synthesis, Structural Activity Relationship, Molecular Modeling and In Vitro Biological Evaluation of New Urea Derivatives with Incorporated Isoxazole and Thiazole Moieties as Anticancer Agents

2019

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“…237 To the search of potent anticonvulsant agents by targeting hCA isoforms several novel chemical entities have been developed and these compounds were shown effective anticonvulsant action in various in vivo models of epilepsy. 234,237,248 Our research group has designed and synthesized benzenesulfonamide-based potent and selective hCA II/hCA VII inhibitors and their anticonvulsant activity were assessed by using Maximal electroshock (MES-test) and pentylenetetrazol (sc-PTZ test). The result of this investigation exposed that compounds 383, 384, and 385 (Potent hCA II/hCA VII in inhibitors) showed excellent anticonvulsant activity in MES as well as sc-PTZ test (Figure 28).…”

Section: Cais With Anticonvulsant Actionmentioning

confidence: 99%

“…But other mechanisms have been also hypothesized that are blockade of sodium channels, kainate/AMPA receptors, and intensification of GABA-ergic transmission. 234,237,350,351 AAZ alone or in combination with dexamethasone was shown to be effective in the preclusion and management of mountain sickness and high altitude associated cerebral edema, due to the enhanced arterial oxygen concentrations after red blood cell/brain enzyme inhibition by AAZ. 352 Use of AAZ has been also noticed in the treatment of hydrocephalus by inhibition of CAs present in choroid plexus.…”

Section: Miscellaneous Pharmacological Actions Of Caismentioning

confidence: 99%

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Mishra

Tiwari

Supuran

2020

Medicinal Research Reviews

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188

166

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Carbonic anhydrases (CAs, EC 4.2.1.1) are widely distributed metalloenzymes in both prokaryotes and eukaryotes. They efficiently catalyze the reversible hydration of carbon dioxide to bicarbonate and H + ions and play a crucial role in regulating many physiological processes. CAs are wellstudied drug target for various disorders such as glaucoma, epilepsy, sleep apnea, and high altitude sickness. In the past decades, a large category of diverse families of CA inhibitors (CAIs) have been developed and many of them showed effective inhibition toward specific isoforms, and effectiveness in pathological conditions in preclinical and clinical settings. The discovery of isoform-selective CAIs in the last decade led to diminished side effects associated with off-target isoforms inhibition. The many new classes of such compounds will be discussed in the review, together with strategies for their development. Pharmacological advances of the newly emerged CAIs in diseases not usually associated with CA inhibition (neuropathic pain, arthritis, cerebral ischemia, and cancer) will also be discussed.

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“…Sulfonamides, being antibacterial, having the prominent mechanism of action including attachment of sulfonamides with the dihydropteroate synthetase (DHPS) enzyme and alteration of bacterial pathways of folic acid synthesis in few eukaryotic cells, but in human beings, this mechanism is not followed [3,4]. The sulfonamides have been recognized due to various reported biological activities such as anticancer [5][6][7][8][9], anti-Alzheimer [10,11], anti-tubercular [12,13], antimicrobial [14][15][16][17], anti-inflammatory [18], carbonic anhydrase inhibitors [19][20][21][22], antidiabetic [11], anticonvulsant [23], and antimalarial [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Biological Evaluation, Qsar and Molecular Modeling Studies of 2,4-Dichlorobenzoic Acid Derivatives as Antimicrobial Agents

Thakral

Singh

2019

Asian J Pharm Clin Res

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Objective: The aim of this study was to evaluate 2,4-dichlorobenzoic acid derivatives as antimicrobial agents through in vitro, QSAR and molecular docking studies. Methods: The compounds were subjected to in vitro antimicrobial screening by test tube dilution method and the structural characteristics governing the antimicrobial potential were studied using QSAR methodology. These compounds were also screened for docking simulation to find out binding confirmation of reported compounds with PDB 1aj0 and 5fsa using AutoDock tools and discovery studio. Results: The antimicrobial evaluation data indicated that compounds 13 and 18 were found to be the most effective against all the bacterial strains and Aspergillus niger while compounds 1 and 14 exhibited more antifungal potential against Candida albicans. QSAR studies confirmed the role of molar refractivity and Balaban index (J) as controlling parameters for antimicrobial potential. Molecular modeling study revealed that compounds interact with the active site of PDB by hydrophobic, hydrogen bonding, and Van der Wall interactions. Conclusion: These test compounds were identified as potent candidates for the control of microbial strains tested, and structural relationship with activity may provide valuable information for further design and synthesis of compounds with antimicrobial potential.

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Design, synthesis and biological evaluation ofN-(5-methyl-isoxazol-3-yl/1,3,4-thiadiazol-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamides as human carbonic anhydrase isoenzymes I, II, VII and XII inhibitors

Cited by 26 publications

References 53 publications

Facile Synthesis, Structural Activity Relationship, Molecular Modeling and In Vitro Biological Evaluation of New Urea Derivatives with Incorporated Isoxazole and Thiazole Moieties as Anticancer Agents

Facile Synthesis, Structural Activity Relationship, Molecular Modeling and In Vitro Biological Evaluation of New Urea Derivatives with Incorporated Isoxazole and Thiazole Moieties as Anticancer Agents

Progress in the development of human carbonic anhydrase inhibitors and their pharmacological applications: Where are we today?

Biological Evaluation, Qsar and Molecular Modeling Studies of 2,4-Dichlorobenzoic Acid Derivatives as Antimicrobial Agents

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