QSAR STUDIES ON HUMAN CARBONIC ANHYDRASE II INHIBITORS

Carbonic anhydrase II is one of the forms of human α carbonic anhydrases which are ubiquitous metalloenzymes that catalyze inter-conversion of carbon dioxide and water to bicarbonate and proton, overexpression of which leads to disorders such as glaucoma. 2D and 3D Quantitative Structure Activity Relationship studies were carried out on previously synthesized series of sulfanilamide derivatives by VLife MDS software using stepwise variable, multi-linear regression and k-nearest neighbor molecular field analysis methods. 2D-QSAR model depicts contribution of halogens (such as chlorine and fluorine), methylene and oxygen atoms to inhibition of human carbonic anhydrases II activity. Using k-nearest neighbor molecular field analysis method two 3D-QSAR models (model A and B) were generated from which model A was found to be the best validated model with q2 (0.9494), pred_r2 (0.7367) and q2 _ se (0.2037). It displayed the fact that the inhibitory action of sulfanilamide derivatives against human carbonic anhydrases II is influenced by hydrophobicity and electro positivity.

New Carbonic Anhydrase-II Inhibitors from Marine Macro Brown Alga Dictyopteris hoytii Supported by In Silico Studies

In continuation of phytochemical investigations of the methanolic extract of Dictyopteris hoytii, we have obtained twelve compounds (1–12) through column chromatography. Herein, three compounds, namely, dimethyl 2-bromoterepthalate (3), dimethyl 2,6-dibromoterepthalate (4), and (E)-3-(4-(dimethoxymethyl)phenyl) acrylic acid (5) are isolated for the first time as a natural product, while the rest of the compounds (1, 2, 6–12) are known and isolated for the first time from this source. The structures of the isolated compounds were elucidated by advanced spectroscopic 1D and 2D NMR techniques including 1H, 13C, DEPT, HSQC, HMBC, COSY, NEOSY, and HR-MS and comparison with the reported literature. Furthermore, eight compounds (13–20) previously isolated by our group from the same source along with the currently isolated compounds (1–12) were screened against the CA-II enzyme. All compounds, except 6, 8, 14, and 17, were evaluated for in vitro bovine carbonic anhydrase-II (CA-II) inhibitory activity. Eventually, eleven compounds (1, 4, 5, 7, 9, 10, 12, 13, 15, 18, and 19) exhibited significant inhibitory activity against CA-II with IC50 values ranging from 13.4 to 71.6 μM. Additionally, the active molecules were subjected to molecular docking studies to predict the binding behavior of those compounds. It was observed that the compounds exhibit the inhibitory potential by specifically interacting with the ZN ion present in the active site of CA-II. In addition to ZN ion, two residues (His94 and Thr199) play an important role in binding with the compounds that possess a carboxylate group in their structure.

CA2 expression associates with survival in triple negative breast cancer.

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of carbonic anhydrase II, encoded by CA2 when comparing the primary tumors of triple negative breast cancer patients dead or alive. CA2 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.