RUTIN RESTORE BIOCHEMICAL CHANGES, OXIDATIVE STRESS AND BETATROPHIN LEVEL IN STZ-INDUCED DIABETIC RATS

Objective: Diabetes mellitus (DM) is associated with long-term damage, dysfunction, of various organs. Study aims to assessrole of rutin on experimentally induced diabetes. Methods: 50 adult male albino rats divided into 5 groups. Group I (control group, rats were orally administered with 1 ml saline daily). Group II (DMSO group, rats were orally administered with 0.2 % DMSO for 60 d orally). Group III (positive control, animals were injected intraperitoneally with 60 mg/kg b. wtstreptozotocin followed by intraperitoneal injection with 120 mg/kg b. wt of Nicotinamide after 15 min). Group IV (therapeutic group, diabetic rats treated with 100 mg/kg b. wt of rutin for 60 d orally). Group V (standard group, diabetic animals treated with 100 mg/kg b. wt of metformin for 60 d orally). At the end of the experimental period blood serum and plasma, liver, kidney and pancreatic tissues were collected. Results: Diabetic rats showed a significant increase in plasma glucose, serum urea, creatinine, cholesterol and triglyceride. Also, induced oxidative stress as pointed out an increase in MDA level, decrease in GSH level, GST and CAT activities in compared to control group. Also, showed an increase in plasma and tissues levels of betatrophin. Oral administration of rutin cause decrease in elevated biochemical and oxidative stress parameters. Also, decrease betatrophin level when compared with diabetic rats. Our results were confirmed by histopathological examination of different tissues. Conclusion: This study suggests thatrutinexihibitsantihyperglycemic and antioxidant activity in streptozotocin-induced diabetic rats

Biochemical Characterization and Antimicrobial Activity Against Some Human or Phyto-Pathogens of New Diazonium Heterocyclic Metal Complexes

String of vanadium (IV), zirconium (IV), palladium (II), platinum (IV) and uranium (VI) chelates of 2-cyano-2-[(2- nitrophenyl)hydrazono]thioacetamide (Cnphta) were prepared and characterized by physicochemical, spectroscopic and thermal analyses. The formulae of the isolated solid complexes were assigned as [VO- (Cnphta)2(H2O)]SO4 ·5H2O (1), [ZrO(Cnphta)2(H2O)]Cl2 ·4H2O (2), [Pd(Cnphta)2]Cl2 (3), [Pt(Cnphta)2Cl2]Cl2 (4) and [UO2(Cnphta)2](NO3)2 ·5H2O (5). The infrared assignments clearly showed that Cnphta ligand coordinated as a bidentate feature through the hydrazono nitrogen and the thioacetamide nitrogen for V(IV), Zr(IV) and U(VI) but displayed different behavior for Pd(II) and Pt(IV). Results of the molar conductivities measurements showed that the metal complexes were electrolytes in contrast with Cnphta ligand. The interpretation, mathematical analysis and evaluation of kinetic parameters were also carried out. In addition, the studied ligand and its new chelates were tested for their antimicrobial activity against some human or phytopathogenic microorganisms. The new metal complexes explicated promising antibacterial activity against all tested bacteria especially Staphylococcus aureus and Bacillus subtilis. Regarding the antifungal activity, all metal complexes were able to inhibit the mycelium growth of both tested pathogenic fungi. In particular Zr(IV) and Pt(IV) complexes showed the highest significant fungicidal effect against A. fumigatus similar to positive contro

Design, synthesis and anticancer evaluation of novel pyrazole, pyrazolo[3,4-d]pyrimidine and their glycoside derivatives

The chalcone derivatives 3a,b were cyclized upon reaction with thiourea to give the pyrazolo[3,4-d]pyrimidine derivatives 5a,b. Condensation of 5a,b and their hydrazide derivatives 8a,b with cyclic and acyclic glucose gave the condensed S- andN-glycosides 7a,b and 9a,b, respectively. Reaction of 3b with ethyl cyanoacetate followed by reaction with cyclic glucose afforded a mixture of the O- and/or N-glycoside isomers 12 and 13, respectively. The pyrazolo[3,4-c]pyrazole derivative 14 was also obtained from the reaction of 3b with hydrazine hydrate. A number of the synthesized compounds were screened for their antitumor activity against three different tumor cell lines HEPG2 (liver), HCT116 (colon) and MCF-7 (breast) with a docking study against CDK2

Design, Synthesis, Biological Evaluation, 2D-QSAR Modeling, and Molecular Docking Studies of Novel 1H-3-Indolyl Derivatives as Significant Antioxidants

Novel candidates of 3-(4-(thiophen-2-yl)-pyridin/pyran/pyrimidin/pyrazol-2-yl)-1H-indole derivatives (2–12) were designed by pairing the pyridine/pyrane/pyrimidine/pyrazole heterocycles with indole and thiophene to investigate their potential activities as (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) inhibitors. The purpose of these derivatives’ modification is to create high-efficiency antioxidants, especially against ABTS, as a result of the efficiency of this set of key heterocycles in the inhibition of ROS. Herein, 2D QSAR modeling was performed to recommend the most promising members for further in vitro investigations. Furthermore, the pharmacological assay for antioxidant activity evaluation of the yielded indole-based heterocycles was tested against ABTS (2,2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid); by utilizing ascorbic acid as the standard. Candidate 10 showed higher antioxidant activity (IC50 = 28.23 μg/mL) than ascorbic acid itself which achieved (IC50 = 30.03 μg/mL). Moreover, molecular docking studies were performed for the newly designed and synthesized drug candidates to propose their mechanism of action as promising cytochrome c peroxidase inhibitors compared to ascorbic acid as a reference standard. Our findings could be promising in the medicinal chemistry scope for further optimization of the newly designed and synthesized compounds regarding the introduced structure-activity relationship study (SAR) in order to get a superior antioxidant lead compound in the near future

Synthesis, molecular docking study, and biological evaluation and of new thiadiazole and thiazole derivatives incorporating isoindoline-1,3-dione moiety as anticancer and antimicrobial agents

To highlight the importance of thiazole and thiadiazole derivatives in the progression of cancer and microbial treatments and to aid in drug design, we have synthesized a new series of 1,3,4-thiadiazole and 1,3-thiazole derivatives. These were created by a two-step reaction process: initially, 2-(4-(2-bromoacetyl)phenyl)isoindoline-1,3-dione was reacted with potassium thiocyanate, and then the resulting thiocyanate intermediate was coupled with aryl diazonium salts to produce iminothiadiazole derivatives. These derivatives served as crucial intermediates for further synthesizing a range of thiadiazole derivatives using different reagents. Additionally, treating 2-(4-(2-bromoacetyl) phenyl)isoindoline-1,3-dione with thiourea resulted in aminothiazole derivatives. These were further coupled with arenediazonium chloride to form 5-arylazoaminothiazole derivatives. All the synthesised compounds were characterised using IR, 1H NMR and 13C NMR spectrum data, as well as physical data. The assessment of the synthesized compounds on the HCT-116 human colon cancer cell line has yielded promising results. Specifically, compounds 3a, 3b, 4b, 5b, 6b, and 9b have shown noteworthy efficacy, suggesting their potential as anticancer agents. These compounds have demonstrated a greater potency compared to the standard drug, doxorubicin, highlighting their significance in cancer treatment research. The study assessed the activity of various newly synthesized compounds against diverse microorganisms, including bacteria and fungi. Notably, two of these compounds, specifically 4b and 7b, exhibited significant efficacy against both gram-positive and gram-negative bacteria, surpassing the performance of a standard antibacterial reference agent. Furthermore, molecular docking of new products revealed interactions with enzyme binding sites, aligning with in vitro findings. Additionally, in-silico studies confirmed their favourable oral bioavailability through ADME profiling