Some characteristics of new and innovative COX inhibitor derivatives: Potent hCA‐I and hCA‐II inhibitors supported by molecular docking studies

Abstract

In this study, two novel metallophthalocyanines (ZnPc and CoPc) were synthesized using the corresponding metal salts 4‐(4‐(4‐[4‐chlorophenyl]‐5‐methylisoxazol‐3‐yl)phenoxy)‐phthalonitrile (11), prepared from the reaction of 4‐nitrophthalonitrile and 4‐(4‐[4‐chlorophenyl]‐5‐methylisoxazol‐3‐yl)phenol (9). These metallophthalocyanines (MPcs) showed quite solubility in organic solvents such as dichloromethane (DCM), tetrahydrofuran (THF), dimethyl formamide (DMF), and dimethylsulfoxide (DMSO). The novel compounds 11a and 11b have been characterized using their UV–Vis, FT–IR, 1H NMR, 13C NMR, X‐Ray, and MALDI–TOF mass spectra. Supporting information cocerning with the study has been supplied. Photochemical, photophysical, and cyclic voltagram properties of these novel 4‐(4‐(4‐[4‐chlorophenyl]‐5‐methylisoxazol‐3‐yl)phenoxy substituted metallophthalocyanines (11a and 11b) were determined in DMF. DNA binding, metal chelating effect assay, and DPPH [2,2‐diphenyl‐1‐picrylhydrazyl hydrate] radical scavenging assay and electrochemical studies of MPcs were investigated. Further, the inhibitory effects of the COX‐inhibitor based novel metallophthalocyanines (11a and 11b) and their ligands (10 and 11) were examined on human erythrocyte carbonic anhydrase I (hCA‐I) and II (hCA‐II) isoenzymes, and the synthesized molecules exhibited very strong inhibitory effects on both isoforms. In addition, the hCA‐I and hCA‐II inhibition potential of Zn (II) and Co (II) Phthalocyanine complexes was supported by molecular docking studies. The binding interaction of metallophthalocyanines complexes 11a, 11b enzymes were analyzed in detail.

Carboxylate‐ and Sulfonate‐Containing Quinazolin‐4(3H)‐one Rings: Synthesis, Characterization, and Carbonic Anhydrase I–II and Acetylcholinesterase Inhibition Properties

“…The CAII isoenzyme has the highest catalytic activity (Kcat/Km 1.5 × 10 8 M À 1 s À 1 ), and the distribution of these 16 isoenzymes in tissues, their catalytic activities, and their affinities for inhibitors and activators differ. [1,4,6,7] Since CA isoenzymes are associated with many pathological conditions such as obesity, epilepsy, Alzheimer's, cancer, glaucoma, hemolyticanemia, osteoporosis, and neuropathic pain, the determination of specific inhibitors of these isoenzymes has attracted the attention of scientific studies. Today, assorted CA inhibitors such as Acetazolamide (AZA), Methazolamide, Dorzolamide, Brinzolamide, Diclofenamide, Ethoxazolamide, Zonisamide, Indisulam, etc.…”

Influence of Chirality of Benzimidazole Amine Hybrids on Inhibition of Human Erythrocytes Carbonic Anhydrase I, II and Acetylcholinesterase

“…CA isoenzymes were purified from human erythrocytes in one step using CNBr‐activated Sepharose‐4B−L‐tyrosine sulfanilamide affinity chromatography as in our previous studies [40,50,51] . Quantitative protein determination was performed in the purification steps with the Bradford method [52] .…”

“…The product was purified by silica gel column chromatography using AcOEt and hexane (1 : 4) In vitro inhibition studies of 4a, 4b, 4c, and 4d on hCA-I and hCA-II isoenzymes CA isoenzymes were purified from human erythrocytes in one step using CNBr-activated Sepharose-4BÀ L-tyrosine sulfanilamide affinity chromatography as in our previous studies. [40,50,51] Quantitative protein determination was performed in the purification steps with the Bradford method. [52] The purity of isoenzymes was checked with the SDS-PAGE method [53] as in our previous studies.…”

Synthesis and Evaluation of Quinazolin‐4(3H)‐one Derivatives as Multitarget Metabolic Enzyme Inhibitors: A Biochemistry‐Oriented Drug Design

“…Such chemical moieties that can be employed to cure disease are required for the treatment of cancer linked to the abnormal expression of CA II. [11,12] Heterocyclic compounds are of much intention as they are therapeutically and pharmacologically active. These compounds are the building blocks of many pharmaceutical products.…”

“…In addition, it has been discovered that CA‐II is highly expressed in macrophages, where it is crucial for producing hydrogen ions. Such chemical moieties that can be employed to cure disease are required for the treatment of cancer linked to the abnormal expression of CA II [11,12] …”