Identification of potent human carbonic anhydrase IX inhibitors: a combination of pharmacophore modeling, 3D-QSAR, virtual screening and molecular dynamics simulations

Chahal, Varun; Nirwan, Sonam; Pathak, Mallika; Kakkar, Rita

doi:10.1080/07391102.2020.1860132

Cited by 11 publications

(8 citation statements)

References 64 publications

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“…Nef modeling was performed for the target sequence P03407 (HIV-1 group M subtype B isolate ARV2/BRU) and the model was built by us using several servers for protein structure prediction: Phyre2 [37] , iTasser [38] , RaptorX [39] , M4T [40] , SwissModel [41] . The final structure was built using server QA-RecombineIt [30] , as described in [20] .…”

Section: Methodsmentioning

confidence: 99%

“…To initiate the development of inhibitors of Nef:ABCA1 interaction, we relied on the computational strategy, including molecular modeling, virtual screening, docking and molecular dynamics. Such approach has been previously used to discover a number of inhibitors for potential therapeutic applications [26] , [27] , [28] , [29] , [30] . These results identified candidate molecules for future development efforts.…”

Section: Introductionmentioning

confidence: 99%

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Direct interaction between ABCA1 and HIV-1 Nef: Molecular modeling and virtual screening for inhibitors

Adzhubei

Kulkarni

Tolstova

et al. 2021

Computational and Structural Biotechnology Journal

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Direct interaction between ABCA1 and HIV-1 Nef: Molecular modeling and virtual screening for inhibitors

Adzhubei

Kulkarni

Tolstova

et al. 2021

Computational and Structural Biotechnology Journal

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“…Computer-aided drug design approaches were also employed to identify new CA inhibitors. These include the use of pharmacophore modeling, 3D quantitative structure-activity relationship (QSAR), virtual screening, and molecular dynamics simulations 115 . Moreover, non-classical sulfonamide inhibitor design includes molecules of classical sulfonamides linked to a disaccharide (such as sucralose or sucrose) that have the potential to produce effective CAIX inhibitors.…”

Section: Targeting Caix With Small Molecule Inhibitorsmentioning

confidence: 99%

Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies

Kciuk

Gielecińska

Mujwar

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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Carbonic anhydrases IX and CAXII (CAIX/CAXII) are transmembrane zinc metalloproteins that catalyze a very basic but crucial physiological reaction: the conversion of carbon dioxide into bicarbonate with a release of the proton. CA, especially CAIX and CAXII isoforms gained the attention of many researchers interested in anticancer drug design due to pivotal functions of enzymes in the cancer cell metastasis and response to hypoxia, and their expression restricted to malignant cells. This offers an opportunity to develop new targeted therapies with fewer side effects. Continuous efforts led to the discovery of a series of diverse compounds with the most abundant sulphonamide derivatives. Here we review current knowledge considering small molecule and antibody-based targeting of CAIX/CAXII in cancer.

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“…It has been reported in the literature that the expression of CA-IX is related to the migration and invasion of renal cancer, lung cancer, and breast cancer [ 12 ]. CA-IX is expected to be a good tumor marker for predicting tumor recurrence [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Expression and prognostic value of carbonic anhydrase IX (CA-IX) in bladder urothelial carcinoma

Xiang

Chen

et al. 2022

BMC Urol

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Objective To investigate the expression intensity of carbonic anhydrase IX (CA-IX) in bladder urothelial carcinoma and its predictive value for the recurrence after transurethral resection of bladder tumor. Methods A retrospective analysis was made of 194 specimens who underwent transurethral resection of bladder tumors in our hospital from January 2014 to January 2016 and completed follow-up. The expression intensity of CA-IX and the clinical data of the patients were analyzed, and the subjects were divided into positive group and negative group according to the expression intensity of CA-IX. The age, gender, T stage, degree of differentiation, tumor number, tumor diameter, recurrence of each group was analyzed. Logistic univariate and multivariate analysis was used successively to find independent influencing factors for predicting the recurrence of bladder urothelial carcinoma after resection. The Kaplan–Meier survival curve was drawn according to the relationship between CA-IX expression intensity and postoperative recurrence. Results The positive expression rates of CA-IX in bladder urothelial carcinomas were 68.1% (132/194). The positive expression of CA-IX had no statistical significance with age, gender and tumor diameter (P > 0.05), while the positive expression of CA-IX had statistical significance with tumor T stage, tumor differentiation, tumor number and recurrence (P < 0.05); Logistic regression analysis showed that clinical T stage, tumor differentiation, tumor number, and CA-IX expression intensities were independent risk factors for predicting recurrence of bladder urothelial carcinoma after resection (P < 0.05); There were 59 cases of recurrence in the positive expression of CA-IX group, with a recurrence rate of 44.69% (59/132), and 17 cases of recurrence in the negative expression group, with a recurrence rate of 27.41% (17/62). The mean recurrence time of CA-IX positive group was 29.93 ± 9.86 (months), and the mean recurrence time of CA-IX negative group was 34.02 ± 12.44 (months). The Kaplan–Meier survival curve showed that the recurrence rate and recurrence time of patients with positive expression of CA-IX in bladder urothelial carcinomas were significantly higher than those of patients with negative expression of CA-IX. Conclusion CA-IX is highly expressed in bladder urothelial carcinoma, is a good tumor marker, and can be used as a good indicator for predicting the recurrence of bladder urothelial carcinoma after transurethral resection of bladder tumor.

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Identification of potent human carbonic anhydrase IX inhibitors: a combination of pharmacophore modeling, 3D-QSAR, virtual screening and molecular dynamics simulations

Cited by 11 publications

References 64 publications

Direct interaction between ABCA1 and HIV-1 Nef: Molecular modeling and virtual screening for inhibitors

Direct interaction between ABCA1 and HIV-1 Nef: Molecular modeling and virtual screening for inhibitors

Targeting carbonic anhydrase IX and XII isoforms with small molecule inhibitors and monoclonal antibodies

Expression and prognostic value of carbonic anhydrase IX (CA-IX) in bladder urothelial carcinoma

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