Since herpes simplex virus type 1 (HSV-1) infection is so widespread, several antiviral drugs have been developed to treat it, among which are uracil nucleosides. However, there are major problems with the current medications such as severe side-effects and drug resistance. Here we present some newly synthesized cyclic and acyclic uracil nucleosides that showed very promising activity against HSV-1 compared to acyclovir.

Objectives: The continuous reporting of bacterial resistance to antibiotics is an ongoing challenge that can be life-threatening. Actions to develop new chemicals to overcome the bacterial resistance has gained a significant importance. Methods: A series of ketene S,N-acetals 4a-k and their pyrazoles 6a-k were synthesized and their structures were established by spectral data. Membrane permeability predictions and in vitro antimicrobial activity against multi-drug resistant (MDR) Gram-positive bacteria and other microorganisms was determined. The binding affinity with DNA gyrase was assessed using in silico studies in comparison to ciprofloxacin then tthe gyrase inhibition assay was conducted to detect the mode of action. Results: All the synthesized compounds have a good affinity to pass through the phospholipid membrane of Staphylococcus aureus (S. aureus). Compound 6g exhibited the most potent antibacterial activity with MIC values ranged between 16 and 32 µg/mL. The compound also showed a higher binding affinity than ciprofloxacin with DNA gyrase in the in silico studies and this effect was clearly shown by a very good IC50 value of the gyrase inhibition assay. Conclusions: According to our data, compound 6g is a possible candidate to act against MDR bacteria and its main mode of action is through inhibition of the gyrase enzyme, further modifications are still required to enhance its activity.

Background: Hypercholesterolemia leads to cardiovascular diseases that are almost the leading cause of death worldwide. The cholesterol-lowering effect of probiotics is getting increased attention especially that the chemical drugs produce several undesirable side effects. Understanding probiotics' potential effects and choosing the right way to use them requires research into the mechanisms through which they control serum cholesterol. Methods: In this study, we used two lactic acid bacteria (LAB) (Lactococcus lactis ssp. lactis and Pediococcus sp.) that were isolated in a previous work of ours from dairy products and had a high in vitro cholesterol removal activity together with promising antihyperlipidemic effect in vivo. In the laboratory animal experiment conducted on hamsters for studying the antihyperlipidemic effect of probiotics, the livers of the different groups were excised, and the levels of hepatic total cholesterol and Cytochrome P450 Family 7 Subfamily A Member 1 (CYP7A1) were determined. Statistical analyses were conducted by one-way analysis of variance (ANOVA) then post-hoc test. A probability of p < /em>-value < 0.05 was considered statistically significant. Results: Lactococcus lactis ssp. lactis and Pediococcus sp. significantly (p < /em> < 0.05) decreased the hepatic total cholesterol levels by 24.96 % and 35.80 %, respectively and increased hepatic CYP7A1 levels by about 49.60% and 37.84 %, respectively in comparison to the diet-induced hyperlipidemic control group. There was no significant difference between the effect of the two isolates and the reference drug, atorvastatin in the levels of both test parameters. Conclusion: We introduce two potential probiotics with similar effect as atorvastatin on both hepatic total cholesterol and hepatic CYP7A1 levels. Thus, these isolates can act as adjuvant therapy to decrease the atorvastatin dose and consequently its side effects. The possible mechanism for the antihyperlipidemic effect could be through upregulation of hepatic CYP7A1 genes that leads to more bile acid synthesis from cholesterol and consequently decreasing liver cholesterol level.