Nkechi M. Enwerem

Synthesis of 3-[(N-carboalkoxy)ethylamino]-indazole-dione derivatives and their biological activities on human liver carbonyl reductase.

A series of indazole-dione derivatives were synthesized by the 1,3-dipolar cycloaddition reaction of appropriate substituted benzoquinones or naphthoquinones and N-carboalkoxyamino diazopropane derivatives. These compounds were evaluated for their effects on human carbonyl reductase. Several of the analogs were found to serve as substrates for carbonyl reductase with a wide range of catalytic efficiencies, while four analogs display inhibitory activities with IC(50) values ranging from 3-5 microM. Two of the inhibitors were studied in greater detail and were found to be noncompetitive inhibitors against both NADPH and menadione with K(I) values ranging between 2 and 11 microM. Computational studies suggest that conformation of the compounds may determine whether the indazole-diones bind productively to yield product or nonproductively to inhibit the enzyme.

Behavioural Effect of Pavetta crassipes Extract on Rodents

The effects of the ethanol extract of Pavetta crassipes on the central nervous system (CNS) and on actions of some selected centrally acting drugs were studied in mice and rats. These studies were carried out using the spontaneous motor activity (SMA), amphetamine-induced hyperactivity and stereotyped behaviour, pentobarbital-induced hypnosis and exploratory activity, apomorphine-induced climbing and haloperidol-induced catalepsy in rats. The results demonstrated that the extract of P. crassipes dose-dependently decreased SMA in mice and attenuated amphetamine-induced hyperactivity and the different episodes of stereotypic behavioural patterns induced by amphetamine. In addition, the extract decreased the number of head dips in the exploratory activity test and potentiated pentobarbital-induced sleeping time in rats. Furthermore, the extract inhibited apomorphine-induced climbing in mice and potentiated haloperidol-induced catalepsy in rats. Our results suggest that the extract of P. crassipes contains biologically active substance(s) that might be acting centrally through the inhibition of dopaminergic pathway or a system linked to this pathway to mediate the observed pharmacological effects.

Evaluation of the Anticancer Activity of Bioactive Fraction G Extracted from Pavetta crassipes in Malignant Brain Tumor Cell Lines

Objective: Natural products have served as sources of lead compounds that are commonly used in the treatment of human diseases including cancer. Pavetta crassipes has been widely demonstrated to have ethnopharmacological potential in the management of malaria, gastrointestinal conditions, central nervous system behavioral disorders, hypertension, and cancer. The goal of our study was to evaluate the biological and molecular effects of Fraction G, obtained from the plant Pavetta crassipes, on glioblastoma invasive growth and survival. Methodology: The antiproliferative effects of Fraction G, obtained from Pavetta crassipes, was evaluated using the trypan blue exclusion, (3-(4, 5-Dimethylthiazol- 2yl)-2, 5-Diphenyltetrazolium Bromide; MTT), and lactate dehydrogenase (LDH) assays. Flow cytometry and Western blotting analyses were carried out to examine the effects of Fraction G on cell cycle check-points and its effects on epidermal growth factor receptor-mediated signaling of AKT and MAPK pathways. Results: In this paper, we report that the Fraction G obtained from the plant Pavetta crassipes induced a reduction in glioma cell viability and proliferation as well as induced an increase in apoptosis as evidenced by cleaved PARP, increased caspase 3/7 activity, and cell cycle arrest in the G0/G1 check point. Furthermore, we report that Fraction G inhibited the phosphorylation of AKT and MAPK following EGF treatment. Conclusion: Taken together, our results demonstrate that Fraction G has potent inhibitory effects on pathways involved in glioblastoma proliferation and survival.

2,3-Dichloro-5,8-dimeth­oxy-1,4-naphtho­quinone

In the crystal structure of the title compound, C12H8Cl2O4, molecules crystallize in planes parallel to (-204) with an interplanar distance of 3.288 (2) Å [centroid–centroid distance = 3.819 (2) and slippage = 1.932 (2) Å]. The structure features C—H⋯O interactions involving methoxy and aromatic H atoms and the carbonyl O atoms as well as a C—H⋯Cl interaction involving an aromatic H atom. In addition there are short interhalogen contacts between adjoining molecules [Cl⋯Cl = 3.3709 (5) Å].