Sulfonamide derivatives with benzothiazole scaffold: Synthesis and carbonic anhydrase I-II inhibition properties.

The secondary sulfonamide derivatives containing benzothiazole scaffold (1-10) were synthesized to determine their inhibition properties on two physiologically essential human carbonic anhydrases isoforms (hCAs, EC, 4.2.1.1), hCA I, and hCA II. The inhibitory effects of the compounds on hCA I and hCA II isoenzymes were investigated by comparing their IC50 and Ki values. The Ki values of compounds (1-10) against hCA I and hCA II are in the range of 0.052 ± 0.022-0.971 ± 0.280 and 0.025 ± 0.010-0.682 ± 0.335, respectively. Some of these inhibited the enzyme more effectively than the standard drug, acetazolamide. In particular, compounds 5 and 4 were found to be most effective on hCA I and hCA II.

Synthesis and characterization of novel acyl hydrazones derived from vanillin as potential aldose reductase inhibitors.

In the polyol pathway, aldose reductase (AR) catalyzes the formation of sorbitol from glucose. In order to detoxify some dangerous aldehydes, AR is essential. However, due to the effects of the active polyol pathway, AR overexpression in the hyperglycemic state leads to microvascular and macrovascular diabetic problems. As a result, AR inhibition has been recognized as a potential treatment for issues linked to diabetes and has been studied by numerous researchers worldwide. In the present study, a series of acyl hydrazones were obtained from the reaction of vanillin derivatized with acyl groups and phenolic Mannich bases with hydrazides containing pharmacological groups such as morpholine, piperazine, and tetrahydroisoquinoline. The resulting 21 novel acyl hydrazone compounds were investigated as an inhibitor of the AR enzyme. All the novel acyl hydrazones derived from vanillin demonstrated activity in nanomolar levels as AR inhibitors with IC50 and KI values in the range of 94.21 ± 2.33 to 430.00 ± 2.33 nM and 49.22 ± 3.64 to 897.20 ± 43.63 nM, respectively. Compounds 11c and 10b against AR enzyme activity were identified as highly potent inhibitors and showed 17.38 and 10.78-fold more effectiveness than standard drug epalrestat. The synthesized molecules' absorption, distribution, metabolism, and excretion (ADME) effects were also assessed. The probable-binding mechanisms of these inhibitors against AR were investigated using molecular-docking simulations.

Synthesis and Carbonic Anhydrase Inhibition of Novel 2-(4-(Aryl)thiazole-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione Derivatives.

Carbonic anhydrase (CA, EC 4.2.1.1) is a member of the metalloenzyme family. It catalyzes the rapid conversion of carbon dioxide (CO2 ) and water to bicarbonate (HCO3- ) and protons (H+ ) and also plays an important role in biochemical and physiological processes. In this study, a number of novel 2-(4-(aryl)thiazole-2-yl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione derivatives were synthesized and evaluated for their inhibitory characteristics against the human CA isoenzymes I and II (hCA I and hCA II). The structures of the new molecules 8a-i were confirmed by means of IR, 1 H NMR, 13 C NMR, and elemental analysis. These compounds exhibited excellent inhibitory effects, in the low nanomolar range, with Ki values in the range of 27.07-37.80 nM against hCA I and in the range of 11.80-25.81 nM against hCA II. Our findings suggest that the new isoindolylthiazole derivatives have superior inhibitory effect over acetazolamide (AZA), which is used as clinical CA inhibitor with Ki values of 34.50 and 28.93 nM against the hCA I and hCA II isoenzymes, respectively.

Significance of the counteracting oxidative and antioxidative systems in the pathogenesis of laryngeal carcinoma.

OBJECTIVE: To evaluate the parameters of oxidative and antioxidative systems in laryngeal carcinoma for their effects on pathogenesis. METHODS: Blood and plasma samples from 30 patients with laryngeal carcinoma were compared with 15 smokers who were otherwise healthy. The tumour tissue samples of the 30 patients were compared with the adjacent non-tumour-bearing mucosal tissue in which carcinoma was ruled out histologically. Although malondialdehyde was used as the main indicator of oxidative stress, superoxide dismutase, glutathione, and catalase activities were accepted as indicators of the antioxidative defense mechanism. RESULTS: Malondialdehyde was significantly higher in the plasma and blood of patients when compared with those of the control group. Glutathione, superoxide dismutase, and catalase activity levels were measured in blood, and these parameters were significantly higher in the control group (p < .001). All results were found to be statistically significant (p < .001). The malondialdehyde level was also found to be significantly higher (p < .01) in the tumour tissue sample. Among the parameters of the tissue antioxidative defense mechanism, superoxide dismutase levels were determined to be significantly higher (p < .001) in the tumour when compared with the levels in adjacent healthy tissue. However, there was no statistically significant difference between the glutathione and catalase activities of the tumour and non-tumour-bearing tissues (p > .05). CONCLUSION: Although the parameters of the oxidative system appear to increase, the antioxidative variants seem to be reduced in laryngeal carcinoma, with one exception: superoxide dismutase has been found in higher amounts in tumour tissue. These results may reflect the effect of oxidative stress in the pathogenesis of laryngeal carcinoma.