Medicinal Chemistry

Aminolysis of pyrazine-2-carboxylic acid was carried out through an intermediate ethyl pyrazinoate formed by a reaction between pyrazine-2-carboxylic acid and ethanol in the presence of concentrated sulfuric acid under reflux which was then reacted with 2-Aminopyridine under same reflux and the final product proposed theoretically N-(pyridin- 2-yl)pyrazine-2-carboxamide a novel compound was characterized using FTIR spectroscopy, UV/Visible spectroscopy and other physical measurement such as melting point determination, solubility were determined. The FT-IR spectrum of the proposed compound showed absorption shift different from the starting ligand(POA) having (NH) stretch at 3323 cm-1 and (3349 cm-1, 3256 cm-1) of A1 and A2 ligands respectively, (CO) stretch at 1665 cm-1 and 1678 cm-1 for PYPC1 and PYPC2 respectively. The complexes A3 and A5 spectra studies showed a Cu-N, Cu-O, Co-N, and Co-O coordination.

Objective: Helicobacter pylori is a main etiological parameter in chronic active gastritis, gastric duodenal ulcers and gastric malignancy. Particular polyunsaturated fatty acids (PUFA) play roles in inhibitory effect on bacterial propagation. Therefore, this study investigated the protective effects of PUFAs against oxidative stress in patient infected with H. pylori with dyspeptic symptom.
Methods: This study is a double blind clinical trial whose target population was 34 patients infected with H. pylori with dyspeptic symptom. Patients were divided into two groups. The first group was treated with standard therapy without supplement (control), and the second group was treated with Standard Therapy and PUFAs supplement, ω-3, ω-6 and ω-9 (case group) for 2 weeks. Two biopsies from Antrum and body of stomach of all patients were collected before and after the treatment. The biopsy samples were used for quick urease test and measurement of Superoxide Dismutase, Glutathione Peroxidase, and total antioxidant capacity.
Results: In gastric mucosa mean levels of total capacity antioxidant were significantly increased in case group comparing with control group. Also, the mean of superoxide dismutase enzyme activity and glutathione peroxidase activity increased significantly in case group compared with control group (p value <0.001).
Conclusion: The findings revealed that administration of PUFAs supplement can increase total antioxidant capacity and activity of antioxidant enzymes in patients infected with H. pylori.

Some new di(indolyl)thiazolylpyrazoles were prepared from the synthetic intermediate E-1,3-di(1H-indol-3-yl) prop-2-en-1-one under ultrasonication and studied their cytotoxic and antioxidant activities. All the compounds were screened for in vitro cytotoxic activity on three cancer cell lines. The compound 7e exhibited appreciable anticancer activity on NCI-H1299, HCT-166 p53 and PC-3 cancer cell lines. The binding conformation of the target molecules was predicted by docking methodology to explain the biological activities. In fact, the docking studies indicated that could be used as possible leads for therapies against cancers. Amongst all the tested compounds dimethoxy substituted di(indolyl)thiazolylpyrazole (7i) displayed significant radical scavenging activity.

A new class of azolyl indolyl thiazolidinones and azetidinones were prepared from azolyl indolyl Schiff’s bases on reaction with thioglycolic acid and chloroacetyl chloride, respectively under ultrasonication at a frequency of 46 KHz. The chloro substituted thiazolyl indolyl azetidinone (12c) and imidazolyl indolyl azetidinone (13c) are prominent antibacterial agents against B. subtilis whereas 13c is the prominent antifungal agent against A. niger.

Salvia is the largest genus of the Lamiaceae family including about 100 species. Salvia officinalis L. (SO) is one of the most appreciated herbs for richness of the essential oil content and its numerous biologically active compounds. SO has been used in herbal medicine for many centuries. In Islamic literature, it is considered as one of the greatest forms of healing medicine. The leaves of the plant have a wide range of biological activities, such as anti-bacterial, fungistatic, virustatic, anticancer, astringent, eupeptic and antihydrotic effects. Recently, this plant has been focused for its application in traditional medicine as well as to find new neurobiological properties. In this review, the up-todate information on the neurobiological effects of SO on the central nervous system will be reviewed. These include analgesic, memory enhancing, neuroprotective, anticonvulsant, anti-addictive, sedative, anxiolytic, and skeletal muscle relaxant effects. Furthermore, chemical compounds responsible for these effects and the clinical studies on this plant are presented and discussed.

A series of chalcones and respective flavonols have been synthesized to explore their anti-cancer activities. All the chalcones were synthesized by the reaction between aldehydes and substituted acetophenones in typical base carried Claisen-Schmidt condensation and their corresponding flavonols were synthesized by hydrogen peroxide oxidized Flynn-Algar-Oymada epoxidation and cyclization. The synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR and Mass spectrometry and subjected for cytotoxicity test on MCF-7, HT-29 and HeLa cell lines. Maximum number of compounds demonstrated anti-proliferative activity with IC50 in the range of 18.67-174.3 μM. Compound 3h with a chloro group and 1-phenyl-3(4-methoxy phenyl)-4-pyrazolyl moiety and the flavonol 4a with 3-thienyl group were found to be most potent compounds among all the tested compounds against MCF-7 cell lines with IC50 18.67 and 23.79 μM respectively. The most active compound 3h also showed high docking score of -8.825.

Pyrazolyl triazoles (5) were prepared by 1,3-dipolar cycloaddition of diazomethane to Schiff base - 3-ethynyl- N-(heteroarylmethylene)aniline (3), followed by oxidation with I2 in DMSO and studied their antimicrobial activity. The pyridine and dichloropyridine substituted compounds 3d, 5c and 5d are potential antibacterial agents against Bacillus subtilis and 3d is a potential antifungal agent against Penicillium chrysogenum.