In vitro cytotoxic and in vivo antitumoral activities of some aminomethyl derivatives of 2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thiones—Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles

Abstract

The 1,2,4‐triazole and its derivatives were reported to exhibit various pharmacological activities such as antimicrobial, analgesic, anti‐inflammatory, antitumoural, cytotoxic, and antioxidant properties. In this study, a series of triazole compounds (M1‐M10) were evaluated for some biological activities. In vitro qualifications of these compounds on acetylcholinesterase (AChE) and human carbonic anhydrase enzyme activities were performed. Also, their antitumoral activities in human colon cancer (HT29) cell line cultures were examined. In addition, colon cancer experimentation was induced in rats by an in vivo method, and the in vivo anticancer effects of triazole derivatives were investigated. Also, the effects of these derivatives in levels of antioxidant vitamin A, vitamin E, and MDA were studied in rat liver and blood samples. Most of the compounds were found to exhibit significant antioxidant and antitumoral activities. All the compounds had cytotoxic activities on HT29 cell lines with their IC50 values lower than 10 µM concentrations. The low IC 50 values of the compounds are M1 (3.88 µM), M2 (2.18 µM), M3 (4.2 µM), M4 (2.58 µM), M5 (2.88 µM), M6 (2.37 µM), M7 (3.49 µM), M8 (4.01 µM), M9 (8.90 µM), and M10 (3.12 µM).

Synthesis, characterization, biological evaluation, and in silico studies of novel 1,3‐diaryltriazene‐substituted sulfathiazole derivatives

“…The inhibition effects of novel 1,3-diaryltriazene-substituted sulfathiazole compounds (ST1-11) on both hCA (EC 4.2.1.1) isoenzymes (I and II) are described by Verpoorte et al [48] and according to an esterase assay, they were spectrophotometrically recorded at 348 nm. [49,50] Additionally, the AChE (EC 3.1.1.7) inhibitory effects of the novel 1,3diaryltriazene-substituted sulfathiazole compounds (ST1-11) were determined according to the procedure of Ellman et al [51] They were recorded spectrophotometrically at 412 nm using acetylthiocholine iodide as the substrate for the enzymatic reaction, as in previous studies. [52][53][54][55] In addition, the inhibitory effect of novel compounds (ST1-11) on α-GLY (EC 3.2.1.20) activity was determined using the p-nitrophenyl-D-glycopyranoside (p-NPG) substrate according to the analysis of Tao et al [56] and according to previous works.…”

Inhibition profiles of Voriconazole against acetylcholinesterase, α‐glycosidase, and human carbonic anhydrase I and II isoenzymes

“…A significant increase in AChE activity is observed in the early stage of AD, but the activity of BChE increases in later stages of AD . For this reason, AChE is a substantial therapeutic target for the recovery of cholinergic deficits, which is believed to be the hallmark of AD …”

Synthesis, cytotoxicities, and carbonic anhydrase inhibition potential of 6-(3-aryl-2-propenoyl)-2(3H)-benzoxazolones

“…The purification of cytosolic CA isoenzymes (CA I and CA II) was previously described with a simple one-step method by a Sepharose-4B-L tyrosine-sulphanilamide affinity chromatography 42,53,[55][56][57][58] . The protein quantity in the column effluents was determined spectrophotometrically at 280 nm.…”

“…The increase in absorbance of the reaction medium was spectrophotometrically recorded at 348 nm. Also, the quantity of protein was determined at 595 nm according to the method as described previously [55][56][57][58][59][60] . Bovine serum albumin was used as a standard protein.…”

“…For the calculation of K i values, three different concentrations were used. The Lineweaver-Burk curves were drawn and calculations were realised as before [55][56][57][58][59][60] .…”