Medicinal Chemistry

This study aimed to determine whether I/D polymorphism predispose to the development of MI in Tunisia. 50 patients with coronary artery disease complicated by MI and 70 healthy controls were analyzed. Quantitative analyses lipids are founded. DNA was isolated from blood samples. Polymorphisms were assessed by polymerase chain reaction method. Statistical differences between groups were determined by Chi-square test. Compared to controls, cases have significantly higher levels of total cholesterol, triglycerides and LDL-cholesterol and lower level of HDL-cholesterol. There are no significant differences between patients and controls in terms of allelic and genotypic frequencies. However, the frequency of the “I” allele is higher in cases which have 2 MI (p=0.0354). Additionally, a statistically significant association between diabetes, arterial high blood pressure, family history and cigarette smoking with MI was founded (p<0.01). I/D polymorphism of t-PA gene is not associated with MI in this sample of Tunisian population.

Oxidative stress induced by reactive oxygen species (ROS) cause lipid peroxidation at the human erythrocyte membrane with subsequent alterations in the ATPases function. In this study, potential cytoprotective activities of previously reported ”Antioxidant Protein from Curry leaves (APC)’’ in erythrocytes against reactive oxygen (ROS) species generated by pro-oxidants in vitro. The APC prevented red blood cell lysis induced by pro-oxidants; Fe: As (2:20 μmole), Hydrogen peroxide (0.2 mM), and tertiary butyl hydroperoxide (1 mM) upto 97.5, 82.5 and 63%, respectively. Further, APC prevented Fe:As induced K+ leakage in red blood cells up to 95%. The inhibition offered by APC on K+ leakage was comparable to inhibition offered by quinine sulphate, a known K+ channel blocker. Interestingly, the APC at dose dependently restored Na+K+ ATPase and Ca2+Mg2+ ATPase activities of erythrocyte membrane when altered by ROS. The restoration of ATPase activity by APC was two times more than standard antioxidants BHA and α-tocopherol. In conclusion, Curry leaves protein antioxidant is an effective antioxidant in preventing membrane damage and associated functions mediated by reactive oxygen species. It can be further developed as an effective bioprotective antioxidant agent to cellular components.

Current standard pharmacotherapies for anxiety management come with a host of side-effects that may deter the patients from utilizing them. Kava, a traditional beverage from the South Pacific region, has been used as a natural medicine for centuries and has been hypothesized to contain anxiolytic properties. There are a few well-designed, randomly controlled trials that have evaluated the effectiveness of kava or its constituents against anxiety disorders. They have generally shown kava to be effective in managing the disease. However, there has been a serious concern about the hepatotoxic risk of kava, which greatly limits its anxiolytic development and application. This review attempts to summarize the recent anxiolytic trials using kava, the associated hepatotoxicity risks, the potential responsible chemicals for these two activities, and the mechanisms of action. Overall, kava has a great potential to be developed as a natural anxiolytic agent through a systematic approach, but the present form should be used with caution.

Gossypetin is a flavonoid which has anti-mutagenic, anti-atherosclerotic, antioxidant, as well as cytoprotective and antimicrobial effects. The objective of this study was to investigate the cytoprotective role of gossypetin (GP) against cyclophosphamide (CP) toxicity in the human lymphocyte culture. Cytotoxic, necrotic and apoptotic effects of CP (1mM), GP (25, 50 and 100 μM) and combination of them (CP+GP) were studied by using MTT assay and Flow cytometry analysis. It was detected that CP significantly decreased cell viability rate via arresting cell cycle and increasing apoptosis/necroptosis. However, GP treatment reduced negative effects of CP at different concentrations. The most effective concentration of GP against CP toxicity was 25 μM. This concentration GP increased live cell number and cell viability, in addition decreased necrotic and late apoptotic cell quantity which were treated with CP. These results suggest that GP could attenuate the cytotoxic effects of CP and protect the healthy cells when it is used during chemotherapy.

Microbial resistance to existing antimicrobial agents remains a global challenge. In recent years, there has been a significant upsurge in the search for newer antimicrobial agents from nature with plants becoming the major focus in most parts of the world due to the vast availability of plants, which have not been screened for their antimicrobial activity. Hence, the study investigates the antimicrobial properties of aqueous aerial part extract of Phyllanthus muellerianus (PLE) and its major constituent, geraniin. The agar well diffusion and micro-dilution methods as well as time-kill kinetic studies were used to determine the antimicrobial activity of PLE and geraniin against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Bacillus subtilis NCTC 10073, Streptococcus pyogenes (clinical isolate) and Candida albicans (clinical isolate). The mean zones of growth inhibition for PLE and geraniin were in the range of 12.0 ± 0.0 to 22.7 ± 0.3 and 12.0 ± 0.0 to 21.6 ± 0.3 mm, respectively. MIC of both PLE and geraniin ranged from 0.31 to 5 and 0.08 to 1.25 mg/mL (90 to 1310 μM), respectively whiles the minimum cidal concentrations were 5.0 to 50.0 and 2.5 to 10 mg/mL (2.62 to 10.5 mM), respectively. The time-kill kinetics study showed that PLE and geraniin may act as microbiostatic agents. Preliminary phytochemical screening of PLE showed the presence of alkaloids, glycosides, saponins, tannins, flavonoids and terpenoids. The observed antimicrobial activity of the extract, PLE, may be due in large proportion to its major constituent, geraniin.

This study investigates the causal-relationships between human capital and economic growth, and between infrastructure and economic growth in Arab World countries. The study covers the period from 1974 to 2013 using annual data obtained from the World Bank. Most importantly, the study uses advanced Granger causality for panel data with fixed coefficients which introduced by Venet and Hurlin. The full sample has been divided into a sub-groups according the income level, namely, rich countries and non-rich countries, to check if there any existence of the structural differences. The results indicate that the causal-relationships between variables of interest are highly heterogeneous in Arab World. However, there is a feedback relationship between human capital and economic growth and between infrastructure and economic growth in the full sample countries and rich countries group. Also, the results found a oneway causality running from economic growth to human capital and infrastructure in non-rich countries group.

An accurate, simple, fast, and good sensitive Spectrophotometric method have been developed for the determination of Carteolol based on the formation of complex (ion-pair complexes) between the Carteolol (CRT) and Alizarin yellow R Sodium salt (AR) at pH=11.20. This reaction produces a complex red color which is absorbed maximally at 500 nm. Beer’s law was obeyed in the range of 1.80-197.30 ug/mL with molar absorptivity of 1.7663×103 L mole-1cm-1. The effects of analytical parameters on the reported system were investigated. The results were validated statistically. The proposed method was applied to commercially available tablets. Interferences of the other ingredients and excipients were not observed.

Several Diindolyl alkanes and their derivatives have been isolated from plant and marine sources. Among the various derivatives of indoles, Diindolyl methanes have wide medicinal applications such as to induce apoptosis in human cancer cells, antibacterial, Anti-inflammatory, antiviral and hormonal control activities. Therefore, they play essential role in marine as well as terrestrial living systems. In present studies we report novel class of Diindolyl methanes prepared from natural phenolic monoterpenoids, via ortho formylation of phenolic monoterpenoids (Carvacrol, Thymol and Eugenol), followed by synthesis, characterization, anticancer, antioxidant and α-amylase inhibitory activities. All the synthesized derivatives show moderate anticancer activities against human breast cell line MCF7, good antioxidant and α-amylase inhibitory activities using DPPH and α-amylase assay respectively.

In the present work, a new series of different 4-{[4-(2-furoyl)-1-piperazinyl]methyl}-N-(substituted-phenyl) benzamides (5a-h) have been synthesized as possible therapeutic agents for the treatment of Alzheimer’s disease. The structural confirmation of all the synthesized compounds was carried out by their IR, 1H-NMR and EI-MS spectral data. Enzyme inhibition activity was performed against butyrylcholinestrase enzyme, which revealed that, 4-{[4-(2-furoyl)-1- piperazinyl]methyl}-N-(4-ethylphenyl)benzamide (5b) showed excellent IC50 value 0.82 ± 0.001 μM relative to Eserine, a reference standard having IC50 value of 0.85 ± 0.0001 μM. The enhanced potential of this molecule may be attributed to the 4-ethylphenyl group. As the cholinesterase enzyme inhibitors are good targets for Alzheimer’s disease, therefore, the inhibition study of these synthesized molecules was carried out to discover their possible therapeutic effect as target for aforesaid disease.