scholarly journals Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site

Molecules ◽  
2018 ◽  
Vol 23 (5) ◽  
pp. 1045 ◽  
Author(s):  
Srishti Singh ◽  
Carrie Lomelino ◽  
Mam Mboge ◽  
Susan Frost ◽  
Robert McKenna
Keyword(s):  
Carbonic Anhydrase ◽  
Drug Development ◽  
Active Site ◽  
Cancer Drug ◽  
Carbonic Anhydrase Inhibitors

Out of the active site binding pocket for carbonic anhydrase inhibitors

2015 ◽  
Vol 51 (2) ◽  
pp. 302-305 ◽  
Author(s):  
Katia D'Ambrosio ◽  
Simone Carradori ◽  
Simona M. Monti ◽  
Martina Buonanno ◽  
Daniela Secci ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site ◽  
Binding Pocket ◽  
Carbonic Anhydrase Ii ◽  
Carbonic Anhydrase Inhibitors ◽  
Human Carbonic Anhydrase ◽  
Site Binding

2-Benzylsulfinylbenzoic acid binds to human carbonic anhydrase II in a mode completely different from any other class of carbonic anhydrase inhibitors investigated so far.

scholarly journals 2-Mercaptobenzoxazoles: a class of carbonic anhydrase inhibitors with a novel binding mode to the enzyme active site

2020 ◽  
Vol 56 (59) ◽  
pp. 8297-8300
Author(s):  
Murat Bozdag ◽  
Claudiu T. Supuran ◽  
Davide Esposito ◽  
Andrea Angeli ◽  
Fabrizio Carta ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site ◽  
Binding Mode ◽  
Lead Compound ◽  
Carbonic Anhydrase Inhibitors ◽  
Enzyme Active Site

2-Mercaptobenzoxazole represents an interesting lead compound alternative to the classical sulfonamides for the development of selective carbonic anhydrase inhibitors.

Carbonic Anhydrase Inhibitors with Dual-Tail Moieties To Match the Hydrophobic and Hydrophilic Halves of the Carbonic Anhydrase Active Site

2015 ◽  
Vol 58 (3) ◽  
pp. 1494-1501 ◽  
Author(s):  
Rajendra P. Tanpure ◽  
Bin Ren ◽  
Thomas S. Peat ◽  
Laurent F. Bornaghi ◽  
Daniela Vullo ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Active Site ◽  
Carbonic Anhydrase Inhibitors

Computational Studies on Isolated Compounds of Sclerochloa dura; their Efficacy towards Carbonic Anhydrase Inhibition and Anti-cancer Drug Targets

2021 ◽  
Vol 18 ◽  
Author(s):  
Majid Ali ◽  
Asma Zaidi ◽  
Umar Farooq ◽  
Rizwana Sarwar ◽  
Syed Majid Bukhari
Keyword(s):  
Carbonic Anhydrase ◽  
Binding Affinity ◽  
Anticancer Drug ◽  
Active Site ◽  
Drug Targets ◽  
Docking Studies ◽  
Cancer Drug ◽  
Hydroxyl Groups ◽  
Carbonic Anhydrases

Background: In the previous study, we reported the isolation of six compounds from Sclerochloa dura and their in-vitro anti-inflammatory potential by their ability to inhibit phospholipase A2 (PLA2). The objective of the current study is to inspect the effect of these compounds on other expected targets. Methods: For this purpose, various targets and percentage activities are predicted through CoFFer (QSAR) web service. All six compounds under investigation represented 99-100% activity towards carbonic anhydrases (CAs) and 90-100% activity towards anticancer drug targets. As the active site of most of the carbonic anhydrase isozymes is conserved, we selected cytosolic human carbonic anhydrase II (hCA II) for docking studies which is ubiquitous and involved in various human disorders such as glaucoma, pulmonary edema, and epilepsy. Anticancer drug targets include vascular endothelial growth factor receptor 2 (VEGFR2), glucocorticoid receptor (GR), and tyrosine-protein kinase (c-SRC). Interaction of these compounds with hCA II (PDB ID: 3P4V) and anticancer drug targets such as VEGFR2 (ID: 3WZD), GR (ID: 5G5W), and c-SRC (ID: 2SRC) was analyzed through molecular docking studies using MOE (Molecular Operating Environment). Results: The findings suggested that most of these compounds represent excellent binding affinity with hCA II by interacting with zinc-coordinated water molecules through sulfonic acid and hydroxyl groups present in the blends. Similarly, five out of six compounds represented excellent interaction with VEGFR2. Interactions with GR indicated that compounds 2, 3, and 6 binds effectively compared to their co-crystallized ligands. However, among these, the excellent binding affinity with c-SRC was demonstrated by compounds 3 and 6. Conclusion: This study revealed that all these compounds exhibited excellent interaction with the active site of hCA II, however in the light of previously reported data and due to membrane barrier, only compound 1 (due to long hydrophobic tail) and compound 4 (due to absence of bulky carbohydrate groups), can only penetrate inside the cytosol. Compounds 2, 3, 4, and 6 containing bulky carbohydrate moieties cannot penetrate inside the cell, therefore, they might have selective nature towards membrane-bounded tumor-associated hCA IX. This anti-tumor property of compounds was also proved by docking studies with VEGFR2, GR, and c-SRC. Therefore, these compounds may have a synergistic effect against inflammation and cancer. The ADMET studies show that compounds have moderate absorption and permeability along with slight toxicity.

scholarly journals Catechols: a new class of carbonic anhydrase inhibitors

2020 ◽  
Vol 56 (85) ◽  
pp. 13033-13036 ◽  
Author(s):  
Katia D'Ambrosio ◽  
Simone Carradori ◽  
Stefania Cesa ◽  
Andrea Angeli ◽  
Simona M. Monti ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Water Molecule ◽  
Deep Water ◽  
Active Site ◽  
Bound Water ◽  
Binding Mode ◽  
Carbonic Anhydrase Inhibitors ◽  
New Class

Catechols adopt a peculiar binding mode to the CA active site which involves both the zinc bound water molecule and the “deep water”.

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