Stevia is a natural sweetener containing steviol glycosides known to be several times sweeter than sucrose. It is thought to have several beneficial properties though some evidence state it may have detrimental effects. The aim of this study was to investigate the potential beneficial or harmful effects of stevia consumption by exploring its effects on blood pressure, stress hormone levels and anthropometrical markers in A crossover placebo controlled study was conducted on 16 volunteers randomly assigned to consume either stevia or a placebo (sugar) for one week. The measurements were attained on three different occasions and each volunteer was allowed a 3-day initiation period before baseline and in between interventions. The systolic BP increased following stevia intake from 114.5±12.7 to 119.9±12.9mmHg (p<0.001) and diastolic BP from 70.8±9.4 to 75.7±9.6mmHg (p<0.01). Systolic BP increased slightly after the sugar placebo to 115.3±13.6 mmHg (not significant). The mean free cortisol excreted in urine has increased from 91.8±49.1 to 125.7±60.5nmole/day (p<0.01) after the stevia and to 109.1±42.6nmole/day after the placebo (p = 0.210). The ratio of urinary free cortisol/cortisone showed a statistically significant increase from 1.73±0.78 to 2.65±1.03 after stevia (p<0.0001). Salivary cortisol levels have also increased (p<0.01 at AM) after stevia. Placebo intake did not produce a significant change in salivary cortisol. The ratio of salivary cortisol/cortisone during the stevia has increased only in the morning (from 1.22±0.65 to 1.75±0.72, p = 0.05) and a modest increase in the daily average of salivary cortisol/cortisone. There was small insignificant reduction in weight and BMI after stevia intervention (p = 0.246 and p = 0.249 respectively). In conclusion, we have shown that short term stevia intake produced a small but significant increase in BP and effect on body weight and BMI were not significant. The rise in BP might be due to the increase in cortisol levels and cortisol/cortisone ratio indicating that stevia may possibly inhibit 11β-HSD2 enzyme by reducing the conversion of cortisol into cortisone. Therefore caution should be taken by the public who want to consume stevia for longer period of time as a weight reducing sweetener.

Malaria, affecting all continents, remains one of the life-threatening diseases introduced by parasites that are transmitted to humans through the bites of infected Anopheles mosquitoes. Although insecticides are currently used to reduce malaria transmission, their safety concern for living systems, as well as the environment, is a growing problem. Therefore, the discovery of novel, less toxic, and environmentally safe molecules to effectively combat the control of these vectors is in high demand. In order to identify new potential larvicidal agents, a series of 2-aryl-1,2-dihydroquinazolin-4-one derivatives were synthesized and evaluated for their larvicidal activity against Anopheles arabiensis. The in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the compounds were also investigated and most of the derivatives possessed a favorable ADMET profile. Computational modeling studies of the title compounds demonstrated a favorable binding interaction against the acetylcholinesterase enzyme molecular target. Thus, 2-aryl-1,2-dihydroquinazolin-4-ones were identified as a novel class of Anopheles arabiensis insecticides which can be used as lead molecules for the further development of more potent and safer larvicidal agents for treating malaria.

A series of 17 compounds (12-16 b) with 2,4,5-trisubstitutedthiazole scaffold having 5-aryl group, 4-carboxylic acid/ester moiety, and 2-amino/amido/ureido functional groups were synthesised, characterised, and evaluated for their carbonic anhydrase (CA)-III inhibitory activities using the size exclusion Hummel-Dreyer method (HDM) of chromatography. Compound 12a with a free amino group at the 2position, carboxylic acid moiety at the 4-position, and a phenyl ring at the 5-position of the scaffold was found to be the most potent CA-III inhibitor (K i ¼ 0.5 lM). The presence of a carboxylic acid group at the 4-position of the scaffold was found to be crucial for the CA-III inhibitory activity. Furthermore, replacement of the free amino group with an amide and urea group resulted in a significant reduction of activity (compounds 13c and 14c, K i ¼ 174.1 and 186.2 lM, respectively). Thus, compound 12a (2-amino-5-phenylthiazole-4-carboxylic acid) can be considered as the lead molecule for further modification and development of more potent CA-III inhibitors.

Background: Recently, a series of 15 compounds with 2,4,5-trisubstitutedthiazole scaffold having 2- amino/amido/ureido functional groups attached with 5-aryl and 4-carboxylic acid/ester groups (1-15) were reported from our research group as novel potential inhibitors of carbonic anhydrase III (CA III) enzyme. Several research studies revealed the potential role of CA inhibitors as anticancer agents, giving us the impetus to further explore these compounds for their potential as anticancer agents. Objectives: The objective of this study is to investigate the potential of 2,4,5-trisubstitutedthiazole derivatives (1-15) for their possible cytotoxic activity (in vitro) and to calculate (in silico) the absorption, distribution, metabolism, excretion and toxicity (ADMET) properties to evaluate the drug-likeness of these compounds. Methods: Cytotoxic activity (in vitro) was carried out on two breast cancer cell lines (MCF7 and MDA231), and lymphoblastoid human erythroleukemia cell line (K562) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Doxorubicin was used as a positive control. ADMET properties were calculated (in silico) using QikProp module of Schrodinger. Results: Compounds 6 and 9 with a phenylureido group at 2-position, and a methyl-carboxylate moiety at 4-position having para-tolyl and benzyl moiety, respectively at the 5-position of the thiazole ring showed significant cytotoxicity against all the three cell lines. In particular, compound 6 with para-tolyl group at 5-position, exhibited most potent inhibitory effect on the viability of MCF7, MDA231 and K562 cells, with IC50 values of 22, 26 and 11 µM, respectively. Notably, all the highly active compounds possess phenyluriedo group at 2-position with a methyl ester group at 4-position, indicating the probable role of these substituents in the target interaction and inducing cytotoxicity. Interestingly, compounds 1-4 and 10-13 with a free amino group at 2-position did not show any cytotoxic effect on K562 cell line, while exhibiting mild to moderate cytotoxicity against the MCF7 and MDA231 cell lines. However, none of the tested compounds showed any activity against normal human dermal fibroblast cells indicating the safety/tolerability of the examined concentrations. Furthermore, these compounds also exhibited satisfactory ADMET properties (in silico), without violating the Lipinski’s rule of five. Conclusion: The most active compounds 6 and 9 predicted to have good oral absorption and low human serum protein binding, exhibiting no reactive functional group and probable CNS activity compared with 95% of the known oral drugs as predicted (in silico) by QikProp. Thus, compounds 6 and 9 can be considered as lead molecules for further modification and discovery of novel anticancer agents with nanomolar potency.

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