Synthesis of 3-hydroxypyridin-4-one derivatives bearing benzyl hydrazide substitutions towards anti-tyrosinase and free radical scavenging activities.

Tyrosinase is a vital enzyme in the biosynthesis of melanin, which has a significant role in skin protection. Due to the importance of the tyrosinase enzyme in the cosmetics and health industries, studies to design new tyrosinase inhibitors have been expanded. In this study, the design and synthesis of 3-dihydroxypyridine-4-one derivatives containing benzo hydrazide groups with different substitutions were carried out, and their antioxidant and anti-tyrosinase activities were also evaluated. The proposed compounds showed tyrosinase inhibitory effects (IC50) in the 25.29 to 64.13 µM range. Among all compounds, 6i showed potent anti-tyrosinase activity with an IC50 = 25.29 µM. Also, the antioxidant activity of derivatives by using DPPH radical scavenging indicates an EC50 value between 0.039 and 0.389 mM. Molecular docking studies were performed to reveal the position and interactions of 6i as the most potent inhibitor within the tyrosinase active site. The results showed that 6i binds well to the proposed binding site and forms a stable complex with the target protein. Furthermore, the physicochemical profiles of the tested compounds indicated drug-like and bioavailability properties. The kinetic assay revealed that 6i acts as a competitive inhibitor. Also, for the estimation of the reactivity of the best compound (6i), the density functional theory (DFT) was performed at the B3LYP/6-31+G**.

Design, synthesis, in silico ADME, DFT, molecular dynamics simulation, anti-tyrosinase, and antioxidant activity of some of the 3-hydroxypyridin-4-one hybrids in combination with acylhydrazone derivatives.

Tyrosinase is the rate-limiting enzyme in synthesizing melanin. Melanin is responsible for changing the color of fruits and vegetables and protecting against skin photo-carcinogenesis. Herein, some of the hybrids of 3-hydroxypyridine-4-one and acylhydrazones were designed and synthesized to study the anti-tyrosinase and antioxidant activities. The diphenolase activity of mushroom tyrosinase using L-DOPA assayed the inhibitory effects, and the antioxidant activity was assessed using DPPH free radical. The synthesized derivatives were confirmed using 1H-NMR, 13C-NMR, IR, and Mass spectroscopy. Among analogs, compound 5h bearing furan ring with IC50=8.94 µM was more potent than kojic acid (IC50=16.68 µM). The pharmacokinetic profile of the compounds showed that the tested compounds had suitable oral bioavailability and drug-likeness properties. The molecular docking studies showed that compound 5h was located in the tyrosinase-binding site. Also, the molecular dynamics simulation was performed on compound 5h, proving the obtained molecular docking results. At the B3LYP/6-31 + G** level of theory, the reactivity descriptors for 5 g and 5h were investigated using DFT calculations. Also, IR frequency was calculated to verify DFT results with experimental data. The electrostatic potential energy of the surface and the HOMO and LUMO molecular orbitals were also studied. It agrees with experimental results that the 5h is a soft molecule and ready for chemical reaction with other interacting molecules.Communicated by Ramaswamy H. Sarma.

PCR-based detection of Toxoplasma gondii from cattle in southern Iran.

OBJECTIVE: Toxoplasma gondii is a protozoan parasite that is widely prevalent in most warm-blooded vertebrates. Humans mainly become infected by eating raw or undercooked meat. This study was designed to investigate the infection of cattle with T. gondii in Jahrom, southern Iran. METHODS: Tissue samples consisting of heart, diaphragm, and tongue were collected from 125 slaughtered cattle. DNA samples were extracted from the homogenized tissues. T. gondii was detected and genotyped using nested-polymerase chain reaction (Nested-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based on GRA6 and SAG2 (3', 5' terminal regions) genes, respectively. RESULTS: The prevalence of T. gondii DNA was 56% in cattle. The most infected tissue was the diaphragm (54.4%) followed by the heart (48.8%) and tongue (43.2%). Type II was the most prevalent genotype (70%) among T. gondii isolates. CONCLUSION: In this study, the high prevalence of T. gondii infection in cattle meat indicates the important role of cattle in the transmission of infection to humans. Therefore, incorporating the correct method of consuming meat in health education programs is crucial to prevent human infection.

A Comparative Study of HOTAIR Expression in Breast Cancer Patient Tissues and Cell Lines.

OBJECTIVE: Recent data suggest that increased levels of the HOTAIR long non-coding RNA (lncRNA) are involved in the development of various types of malignancy, including breast cancer. The aim of present study was to investigate HOTAIR lncRNA expression profile in breast cancer (BC) patients and cell lines. MATERIALS AND METHODS: In this experimental study, expression level of HOTAIR lncRNA was evaluated in BC and normal tissues of 15 patients as well as MDA-MB-231, MCF-7 and MCF-10A cell lines, using quantitative reversetranscription polymerase chain reaction (qRT-PCR). HOTAIR lncRNA expression levels were estimated using 2-ΔΔCt method. Further, receiver operating characteristic (ROC) curve analysis was done to evaluate the selected lncRNA diagnostic potential. The Cox's proportional hazards regression model was performed to evaluate the predictive value of this lncRNA level in BC patients. RESULTS: The results of present study demonstrated no significant difference in the expression of HOTAIR lncRNA in MCF7 and MDA-MB-231 cancer cell lines compared to MCF-10A as normal cell line (P>0.05). However, we observed a significantly increase in the expression of HOTAIR in BC patients compared to normal tissues (P<0.001). Significant associations were found between gene expression and tumour size and margin. We found 91.1% sensitivity and 95.7% specificity of circulating HOTAIR with an area under the ROC curve of 0.969. The Kaplan-Meier analysis indicated significant correlation between HOTAIR expression and overall survival. CONCLUSION: This study demonstrated that expression of HOTAIR is increased in BC and might be associated with its progression. According to these findings, HOTAIR expression could be proposed as biomarkers for BC early diagnosis and prognosis.