Enaminones 9. Further studies on the anticonvulsant activity and potential type IV phosphodiesterase inhibitory activity of substituted vinylic benzamides

Structure-activity relationship studies were employed to synthesize a series of 3- and 3,4-substituted benzamides from 3-amino-2-cyclohexenones. An improved method for the synthesis of benzamides from 3-amino-2-cyclohexenones is presented which provided significantly higher yields (71-79%) for the reported compounds. NMR and X-ray structural analyses were undertaken to note the possible intra- and intermolecular interactions of the synthesized analogs. Molecular modeling studies were used to determine the minimized configuration and were compared to their X-ray structures for correlation. These new entities were evaluated as potential anticonvulsants and type IV phosphodiesterase inhibitors (PDE4).     

Genotoxicity assessment of a pharmaceutical effluent using four bioassays

Pharmaceutical industries are among the major contributors to industrial waste. Their effluents when wrongly handled and disposed of endanger both human and environmental health. In this study, we investigated the potential genotoxicity of a pharmaceutical effluent, by using the Allium cepa, mouse- sperm morphology, bone marrow chromosome aberration (CA) and micronucleus (MN) assays. Some of the physico-chemical properties of the effluent were also determined. The A. cepa and the animal assays were respectively carried out at concentrations of 0.5, 1, 2.5, 5 and 10%; and 1, 5, 10, 25 and 50% of the effluent. There was a statistically different (p < 0.05), concentration-dependent inhibition of onion root growth and mitotic index, and induction of chromosomal aberrations in the onion and mouse CA test. Assessment of sperm shape showed that the fraction of the sperm that was abnormal in shape was significantly (p < 0.05) greater than the negative control value. MN analysis showed a dose-dependent induction of micronucleated polychromatic erythrocytes across the treatment groups. These observations were provoked by the toxic and genotoxic constituents present in test samples. The tested pharmaceutical effluent is a potentially genotoxic agent and germ cell mutagen, and may induce adverse health effects in exposed individuals.     

Facile Synthesis of New Hybrid 2-Quinlolinone Derivatives Structures as Anticancer Drugs for Breast Cancer Treatment

Russian Journal of Bioorganic Chemistry - A new series of hybrid 2-quinolinone derivatives were synthesized and confirmed using IR, 1H NMR, 13C NMR, and elemental analyses. The cytotoxic activities...     

An in vivo evaluation of induction of abnormal sperm morphology in mice by landfill leachates

Although several reports have demonstrated the acutely toxic and genotoxic effects of landfill leachates in microbial organisms, plants and aquatic animals, the effects of pollutants present in these leachates have not been clarified yet in terrestrial animals. This study mainly aimed to evaluate a potential genetic effect of raw and simulated leachates from Orita-Aperin and Oworonsoki landfills in south-west Nigeria by use of the murine sperm-head abnormality test. These landfills neither have a synthetic membrane liner at the bottom, nor a natural layer of compacted soil with the desired hydraulic conductivity, nor a run-off control system. As a result, the leachates produced are discharged into the environment. Samples designated as Orita-Aperin Raw Leachate (OARL), Orita-Aperin Simulated Leachate (OASL), Oworonsoki Raw Leachate (OWRL) and Oworonsoki Simulated Leachate (OWSL) were analyzed in the sperm-head abnormality test at concentrations (v/v) of 1%, 2.5%, 5%, 10% and 25%. Mice were given 0.5 ml sample per day for five consecutive days by intraperitoneal injection. Each dose group comprised seven mice, and a 5-week exposure period was utilized. The data show that the test mixtures induced a dose-dependent, statistically significant increase (P<0.05) in the number of sperm with abnormal morphology. Physico-chemical analysis of the test samples shows that they contained constituents that are capable of inducing mutation in biologic system. The interaction of some of these constituents with the genetic material in the differentiating cells during spermatogenesis may be responsible for these observations. This is relevant in environmental waste management, and for the assessment of the hazardous effects of the chemicals in landfill leachates.     

Fungal and bacterial metabolites of stored maize (Zea mays,L.) from five agro-ecological zones of Nigeria

Seventy composite samples of maize grains stored in five agro-ecological zones (AEZs) of Nigeria where maize is predominantly produced were evaluated for the presence of microbial metabolites with the LC-MS/MS technique. The possible relationships between the storage structures and levels of mycotoxin contamination were also evaluated. Sixty-two fungal and four bacterial metabolites were extracted from the grains, 54 of which have not been documented for maize in Nigeria. Aflatoxin B₁ and fumonisin B₁ were quantified in 67.1 and 92.9 % of the grains, while 64.1 and 57.1 % exceeded the European Union Commission maximum acceptable limit (MAL) for aflatoxin B₁ and fumonisins, respectively. The concentration of deoxynivalenol was, however, below the MAL with occurrence levels of 100 and 10 % for its masked metabolite, deoxynivalenol glucoside. The bacterial metabolites had low concentrations and were not a source of concern. The storage structures significantly correlated positively or negatively (p?<?0.01 and p?<?0.05), respectively with the levels of grain contamination. Consumption of maize grains, a staple Nigerian diet, may therefore expose the population to mycotoxin contamination. There is need for an immediate action plan for mycotoxin mitigation in Nigeria, especially in the Derived Savannah zone, in view of the economic and public health importance of the toxins.     

Factors influencing extract of Hibiscus sabdariffa staining of rat testes

Some plant extracts can be used in biology and medicine to reveal or identify cellular components and tissues. We investigated the effects of time and concentration on staining of histological sections of rat testes by an acidified extract of Hibiscus sabdariffa. An ethanolic extract of H. sabdariffa was diluted using 1% acetic acid in 70% ethanol to stain histological sections of testes at concentrations of 0.2, 0.1 and 0.05 g/ml for 5, 10, 15, 30, 45 and 60 min. The sections of testes were stained deep red. The staining efficiency of H. sabdariffa was greater at a high concentration and required less time to achieve optimal staining. H. sabdariffa is a strongly basic dye that can be used for various diagnostic purposes. Staining time and concentration must be considered to achieve optimal results.     

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 IC₅₀ values ranging from 3–5 μM. 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 μM. 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.     

Frequency of twinning in southwest Nigeria

BACKGROUND:

In the human species, twin is a type of multiple birth in which the mother gives birth to two offspring from the same pregnancy. The occurrence and frequency of twinning, however, varies across human populations. The maternal age, socio-environmental factors, increase in the use of contraceptives, the race of human population, increase in the spontaneous abortion rate, and seasonal variations are among the factors that could influence twinning rate. Information on twinning rates in southwest Nigeria is limited.

AIMS:

This study presents information on the frequency of twinning, as well as its analysis by maternal age, in four urban settings in southwest Nigeria. This is with the aim of extending current knowledge on the frequency of twinning in southwest Nigeria and contributing to the demographic studies in the country.

MATERIALS AND METHODS:

Data on single births and twin births from January 1995 to December 2004 were collected from the Oyo State General Hospital (OSGH), Wesley Guild Hospital (WGH), Obafemi Awolowo University Teaching Hospital (OAUTH), and Ekiti State Specialist Hospital (ESSH) in Ogbomoso, Ilesa, Ile-Ife, and Ado-Ekiti respectively. These were analyzed by year and maternal age groups of 15-19, 20-24, 25-29, 30-34, 35-39, 40-44, and 45-49 years according to the standard method.

RESULTS:

A frequency of twin births of 46.5 per 1000 deliveries and 46.2 per 1000 deliveries was recorded for Ilesa and Ile-Ife respectively. The frequency recorded for Ogbomoso and Ado-Ekiti was 38.5 and 22.1 per 1000 deliveries respectively. The overall average frequency of 40.2 per 1000 deliveries for the four hospitals ranks among the highest recorded rates of twin births in the world. The maternal age group of 25-29 years had the highest occurrence of twin births, while the lowest was recorded in the 45-49 years age group.

CONCLUSION:

This analysis reveals high incidence of twinning in the studied areas and supports previous assertion that the southwestern part of Nigeria has the highest twinning rate in the country and in the whole world. It is our opinion that diet, maternal history of twinning, and some socio-environmental factors may have influenced the results.     

Human sex ratio at birth in South West Nigeria

BACKGROUND:

Human sex ratio at birth differs from one population to the other. This variation has been attributed to cultural practices, seasonal variation, small-family size policy and sex selective technology. Information on secondary sex ratio in Nigeria is limited.

AIMS AND OBJECTIVE:

To analyzed human sex ratio at birth for samples of the Nigerian population in 4 urban settings in Southwest Nigeria, in order to know the trend and to compare the findings with those of previous reports.

MATERIALS AND METHODS:

Data were collected from Obafemi Awolowo University (OAU) teaching hospital at Ile Ife and Wesley Guild hospital at Ilesa, Osun state; General hospital at Ogbomoso, Oyo state and Ekiti state specialist hospital at Ado-Ekiti, Ekiti state. The data consisted of 35 209 live single births recorded between 1995 and 2004. Each set of data was analyzed to determine the sex ratio by year, month and quarterly values. Chi-square analysis was used to determine the deviation of the sex ratios for the years from the average value.

RESULTS:

The annual average ratios of 104.7:100, 102.8:100, 98.9:100 and 100.8:100 were recorded for OAU teaching hospital, Wesley Guild Hospital, General Hospital and Ekiti State specialist hospital, respectively. When pooled together, the average ratio was 102.7:100. This shows some bias for male births. Data also indicates more male birth in the rainy season, suggesting a seasonal variation of sex ratio.

CONCLUSION:

These findings are representative of the populations in southwest Nigeria and are comparable to values obtained for other regions in Nigeria and other populations of African origin.     

Synthesis and MEK1 inhibitory activities of imido-substituted 2-chloro-1,4-naphthoquinones

Mitogen activated protein kinases are of interest as research tools and as therapeutic target for certain physiological disorders. In this study, we found 2-chloro-3-(N-succinimidyl)-1,4-naphthoquinone 6 to be a selective inhibitor of MEK1 with an IC(50) of 0.38 microM. An open-chain homologue, 10, showed selective cytotoxicity against renal cancer in the NCI in vitro tumor screening. Structure-activity relationship study of eight compounds showed the cyclic imido-substituted chloro-1,4-naphthoquinone as more potent and selective MEK1 inhibitors than the open chain homologues. The imido-substituted chloro-1,4-naphthoquinones were synthesized in a straightforward fashion by refluxing 2-amino-3-chloro-1,4-naphthoquinone with the appropriate acid chloride or diacyl dichloride.