As a continuous research for discovery of new COX-2 inhibitors, chemical synthesis, in vitro biological activity and molecular docking study of a new group of 1, 4-dihydropyridine (DHP) derivatives were presented. Novel synthesized compounds possessing a COX-2 SO2Me pharmacophore at the para position of C-4 phenyl ring, different hydrophobic groups (R1) at C-2 position and alkoxycarbonyl groups (COOR2) at C-3 position of 1, 4-dihydropyridine, displayed selective inhibitory activity against COX-2 isozyme. Among them, compound 5e was identified as the most potent and selective COX-2 inhibitor with IC50 value of 0.30 mM and COX-2 selectivity index of 92. Molecular docking study was performed to determine probable binding models of compound 5e. The study showed that the p-SO2Me-phenyl fragment of 5e inserted inside secondary COX-2 binding site (Arg513, Phe518, Gly519, and His90). The structure activity relationships acquired reveal that compound 5e with methyl and ethoxycarbonyl as R1 and COOR2 substitutions has the necessary geometry to provide selective inhibition of the COX-2 isozyme and it can be a good basis for the development of new hits.

In order to determine the most effective hormones on the in vitro oocyte maturation (germinal vesicle breakdown - GVBD) in a hybrid sturgeon bester, ovarian follicles were incubated at the migratory nucleus stage in the presence of several steroids, gonadotropin preparations and forskolin. Occurrence of GVBD and 17,20 b-dihydroxy-4-pregnen-3 –one (DHP) production were followed during an experimental period of one year of germinal vesicle (GV) migration. From all the steroids tested, three progesterone derivatives-17a- hydroxyprogesterone (17aOHP), 17, 20b, 21-trihydroxy-4-pregnen-3-one (17, 20 b, 21- triol), and DHP-were the most potent steroid inducers of GVBD, followed closely by deoxycorticosterone (DOC). No GVBD responses were found in ovarian follicles in July when the GV was still central. The responsiveness increased gradually from then and reached its peak in November when the GV had migrated fully towards the oocyte periphery. Their potencys gradually declined later from December and the oocytes lost their ability to mature the next July when degeneration set in. DHP production by ovarian follicle during successive months of nucleus migration demonstrated a relatively similar pattern of GVBD frequencies. These results indicated again a relevant role for DHP on oocyte maturation in the bester and also suggested that GV localization along with in vitro oocyte maturation assay can be used as practical tools for selecting the appropriate individuals in exogenous induced spawning in bester.

A group of racemic 3-[(2-hydroxyethyl), (2-Methoxyethyl), (2-acetylethyl) or (2-cyanoethyl)], 5- methyl, ethyl or isopropyl-1 ,4-dihydro-2,6-dimethyl-4-(1-methyl-5-nitro-2-imidazolyl)-3,5-pyridinedicarboxylates [XIV-XXV] were prepared by the reaction of 1-methyl-5-nitroimidazol-2- carboxaldehyde [X] with acetoacetic esters [VI-IX] and alkyl 3-aminocrotonate [XI-XIII]. In vitro calcium channel antagonist activities of the tested compounds were determined by their effects on contraction of Guinea Pig Ileal Longitudinal Smooth Muscle (GPILSM) which was induced by carbacol (1.67 x 10-7 M). All compounds exhibited calcium channel antagonist activity (IC5o=10-12 to 10-13M range) comparable to nifedipine as reference drug (IC5o=1.07±0.12 x 10 -11 M).    

Bester, a hybrid sturgeon (Huso huso L. females x Acipenser ruthenus L. males), neither spermiate nor ovulate in the captivity. Thirteen-year-old adult male and female bester were injected with LH-RHa (0.1-0.3 mg/kg B. W.) intramuscularly and spawning status of the treated fish was checked 24-48 hours later. Additionally, changes in serum levels of DHP in both the responded and the non-responded individuals were monitored 0, 1, 3, 6, 9, 12, 24, 48 and 72 hours after the teatment.Between 70-100 percent of the LR-RHa injected males individuals, and 11-40 percent of the females spawned 24-48 hours after the treatment; the rest did not respond to the injection. In the responded males, 3-9 hours after the treatmen1, serum levels of DHP increased; while in the females it occured first after 12-24 hours. In contrast, during the same period, serum levels of DHP remaind low in all non-responded individuals. The present study indicated that using 0.1-1.3 mg/kg B. W. ofLH-RHa can induce oocyte maturation and ovulation in the females and spermiation in the males cultured bester. The results suggested additionally DHP as an appropriated steroid that could be used in the final maturation stage of the gonads.

Two deoxyglucose (DG) derivatives, (a, b)-2-deoxy-2-amino (ethylcarbamate)-D-glucose (ECB-DG) and (a, b) -2-deoxy-2-amino (1, 2-dihydroxypropyl)-D-glucose (DHP-DG), were synthesized and radiolabeled successfully with [99mTc (H2O) 3 (CO) 3] + complex. [99mTc]-ECBDG and [99mTc]-DHP-DG complexes were prepared (96% and 93% radiochemical purities respectively) by using 46 mCi of Na99mTcO4 in 1 mL saline. Radio-HPLC analysis of [99mTc] - ECB-DG at pH = 7.4, revealed that labeling with 99mTc leads to formation of one radiochemical species with tR = 381 second. Three radiochemical species, Na99mTcO4, [99mTc]-DHP-DG and [99mTc (H2O) 3 (CO) 3] + complexes with tR = 342 sec, tR = 567 sec and tR = 1586 sec respectively, were obtained when [99mTc]-DHP-DG complex evaluated by HPLC. Biodistribution of two complexes were studied on normal mice at 10, 30 and 60 min post-injections. Compared to the 18F-FDG, [99mTc] - ECB-DG displayed a 2.8-fold reduction in brain uptake (1.7 ± 0.2 versus 0.61% ± 0.09), whereas [99mTc] -DHP-DG just showed 1.9-fold reduction in heart uptake (2.2 ± 0.05 towards 1.16±0.10) at 1 h post-injection. On the basis of our results, it seems that ECB-DG and DHP-DG analogues could be used as brain and heart imaging agent respectively.