Mohammad S Alorainy’s research while affiliated with Qassim University and other places

Pyrimidines are a well known group of compounds reported to have different biological activities. Prompted from the diversity of its wider use and being an integral part of genetic material, an effort was made to synthesize a novel series of amino-pyrimidine derivatives of pharmaceutical interest by condensing the guanidinyl derivative of nalidixic acid with different chalcones. The structures of all synthesized compounds were established on the basis of IR and 1HNMR spectral studies. All of the new compounds in this series were screened for antimicrobial activity. Gram +ve and Gram -ve strains were used to ascertain the spectrum of activity. ED50 values in the tail flick test were determined and recorded. Analgesic potential of compounds by using tail flick test in SWR male mice have also revealed promising results. All of the derivatives were effective in Gram -ve test against E. coli. None of the compounds show any inhibition of Gram +ve strain S. aureus. m-Bromo substitution derivative of amino-pyrimidines showed appreciable activity against E. coli, while 2,4 dichloro and p-chloro substitution derivatives also demonstrated improved activity. Compound 4 was most potent. The order of potency for these derivatives was 4>5≥6>1>2>7>3. Parallel to antimicrobial activity, m-bromo substitution derivative showed significant (P<0.01) antinociceptive response in comparison to control, and this effect was comparable to aspirin group. Trimethoxy substitution of benzene ring demonstrated moderate activity, whereas p-bromo substitution essentially had no antinociceptive effects in mice. Comparing meta- and para- bromo substitutions, there had been significant (P<0.01) difference in the antinociceptive response of both the bromo-substituted derivatives. It was observed that bromo-substitution at meta- position demonstrated comparatively higher potential for its antibacterial as well as antinociceptive properties.

This study investigated antiepileptic effects of the main constituents of Nigella sativa (NS) seed (i.e. aqueous extract (AE), fixed oil (FO), volatile oil (VO)) and the main components of its VO (i.e. thymoquinone, α-pinene and p-cymene) using pentylenetetrazole (PTZ) and maximal electroshock (MES)-induced convulsions. The potential of these constituents to induce minimal neurological deficit (MND) was also evaluated by using chimney test.Except for the FO, all of the NS seed constituents protected mice effectively against PTZ-induced convulsions. The activity of the VO in this model maybe attributed mainly to its content of thymoquinone and p-cymene and to a lesser extent, α-pinene. VO and its component p-cymene effectively suppressed convulsions induced by MES. The contents of p-cymene present in the effective dose of the VO maybe partially responsible for its anti-seizure effects.All of the NS seed constituents induced varying degrees of MND in the chimney test. MND induced by VO may pertain to its contents of thymoquinone (63%), p-cymene (23%) and α-pinene (<14%). Protective indices of p-cymene and thymoquinone were closer to one, but only in PTZ model.Exploration on the role of receptors suggests that picrotoxin and bicuculline-sensitive GABA receptors, most probably GABAA receptors, mediate an increase in GABAergic response. In the part dealing with the interaction of valproate with thymoquinone, it can be mentioned that thymoquinone increased the potency of valproate in both PTZ and MES models.

Ambrein and epicoprostanol were evaluated for their antioxidant potential in vitro by chemiluminescence (CL), as well as in vivo using lipid peroxides and glutathione levels as indicators in liver tissue of rats treated with adriamycin (doxorubicin) a well known free radicals producing drug. In the in vitro test, the inhibition in CL by ambrein was dose dependent. Both the high concentrations of ambrein (20–40 μg/ml) inhibited CL response significantly (P < 0.05 and P < 0.01, respectively) when compared to control. Similarly two low concentrations (5–20 μg/ml) of epicoprostanol inhibited CL significantly (P < 0.001 and P < 0.01, respectively) in comparison of DMSO control. The high concentration (40 μg/ml) of epicoprostanol behaved exceptionally and caused an increase in CL response that was more than control and significantly (P < 0.001) higher than both the low concentrations. In the in vivo studies adriamycin treatment significantly (P < 0.05) increased malondialdehyde (MDA) and decreased non-protein sulfhydryl (NP-SH) contents in the liver tissue of mice after 5 days treatment. Ambrein (25 and 50 mg/kg) treatment as a solo therapy at both the dose levels significantly (P < 0.001) decreased MDA contents in the liver tissue. On the other hand, in the combined treatment the high dose effectively prevented any rise in MDA contents and it remained around the levels of ambrein alone. In the same experiment, adriamycin declined NP-SH contents significantly (P < 0.001). Ambrein alone at both the dose levels caused a decline (P < 0.01) in NP-SH contents when compared to adriamycin group. But in the combined treatment this decline in NP-SH was significantly (P < 0.05) different from adriamycin alone.

The antiepileptic potential of thymoquinone (TQ) was studied in mice by using pentylenetetrazole (PTZ) and maximal electroshock seizure (MES)-induced convulsion models. In this investigation, the combined treatment of TQ and sodium valproate (SVP) was also studied. The aim of this part was to minimize SVPinduced hepatotoxic implications, by reducing its antiepileptic dose. TQ in both PTZ- and MES- models increased SVP potency. The experiments dealing with the effects of TQ on the of SVP revealed that TQ reduced the of SVP in both the models. However, this potentiation of SVP antiepileptic response was relatively more significant in PTZ model at both 50 and 100 mglkg doses of TQ. Although very well tolerated and effective, SVP is well known for its hapatotoxic implications. In the experiment dealing with subacute treatment, SVP (1300-1500mglkglday in drinking water) for 21 days, produced hepatotoxicity in mice, characterized by elevated serum ALT and AST, reduced levels of non protein sulfhydryls and increase in lipid peroxidation in hepatic cells. Hepato-protection was successfully achieved when TQ (5-5.5mglkglday) was combined with SVP in drinking water for the same duration. The protective activity of TQ was evident by averting any serum ALT rise seen in SVP treatment. Though there is no prevention to the rise in lipid peroxidation in hepatic tissue but the same time a significant recovery in glutathione was evident by TQ joint treatment. However, a combination of TQ and low dose of SVP may be useful strategy to minimize adverse reactions of SVP. From the results of the present study that disclosed a protective role of TQ against SVP toxic damage to the liver, it could be mentioned safely that TQ behaves as an antioxidant and protected liver against its harmful effects. It also protected against the liver enzyme induction seen in the case of SVP alone.