Synthesis, Characterization, Optical Properties, Molecular Modeling and Urease Inhibition Analysis of Organic Ligands and Their Metal Complexes.

Recently, screening of efficient urease inhibitors by employing organic small molecules metalloderivatives interests the scientific community due to their efficacy for treatment of urease triggered health complications. This study comprises the synthesis, urease inhibition activity, optical analysis and molecular modeling of hydrazinecarbothioamide and hydrazinecarboxamide metalloderivatives. Characterization of synthesized materials was done by UV-visible, fluorescence, NMR and FTIR spectroscopic analysis. Metalloderivatization of ligands induce increment in urease inhibition potential and effect was prominent for copper complexes with 10-fold enhancement, cobalt complex with 3.5 fold's enhancement and palladium with 2-fold increment in the inhibition efficacy toward urease when it was compared with reference urease inhibitor. Zinc and iron complexes cause declined urease inhibition activity of the bare ligand. The overall activity of hydrazinecarbothioamide slightly exceeds than that of hydrazinecarboxamide, possibly due to larger complexation ability of sulfur-based ligand in comparison to oxygenated derivatives i.e., hydrazinecarboxamide. The enzyme inhibition kinetics for the most active complexes represent the mixed type urease inhibition for 3a and competitive urease inhibition for 5a, as determined by Lineweaver-Burk plots. The docked scoring values for both the ligands were calculated to be 61.34, 64.72, 56.68, 62.94, 64.98 and 58.98. Three active hydrogen bonds were observed in docking complex upon computational analysis of most potent metallodrug 3a inside active region of targeted protein.

Phytochemical Screening, Anti-Inflammatory, and Antidiabetic Activities of Different Extracts from Caralluma edulis Plant.

The plant Caralluma edulis is traditionally used against diabetes and inflammatory conditions in Pakistan. This study was designed to provide scientific validation of the traditional use of Caralluma edulis. Phytochemicals were extracted from the plant by different solvents (distilled water, methanol, ethanol, and acetone) using the Soxhlet's extraction method. Bioactive compounds were detected by gas chromatography-mass spectrometry (GC-MS). The in vitro anti-inflammatory activities (albumin denaturation, membrane stabilization, and proteinase inhibition) and antioxidant capacity (DPPH scavenging activity, FRAP reducing activity) of different extracts from Caralluma edulis were assessed. The antidiabetic potential of Caralluma edulis plant extracts was determined in acute and subacute diabetic rabbit models. Oxidative stress and enzymatic antioxidant status were also estimated in MDA, CAT, and SOD levels. Results showed that the methanol extract yielded the highest contents of phenolics, flavonoids, alkaloids, and terpenoids. The in vitro anti-inflammatory activity and antioxidant potential of the methanol extract were the highest among the tested solvents. The tested extracts did not show any remarkable antidiabetic activity in the acute diabetic model. However, all tested extracts demonstrated antidiabetic potential in the subacute diabetic model. No adverse effect was observed at the tested dose (200 mg/kg) of Caralluma edulis extracts in experimental animals. It is concluded that methanol is the key solvent for extracting bioactive compounds from Caralluma edulis. The plant can be used against inflammatory disorders and may prove a potential candidate for drug development. Long-term use of Caralluma edulis at the tested dose (200 mg/kg) showed antidiabetic properties in the animal model.

Diaryl azo derivatives as anti-diabetic and antimicrobial agents: synthesis, in vitro, kinetic and docking studies.

In the present study, a series of azo derivatives (TR-1 to TR-9) have been synthesised via the diazo-coupling approach between substituted aromatic amines with phenol or naphthol derivatives. The compounds were evaluated for their therapeutic applications against alpha-glucosidase (anti-diabetic) and pathogenic bacterial strains E. coli (gram-negative), S. aureus (gram-positive), S. aureus (gram-positive) drug-resistant strain, P. aeruginosa (gram-negative), P. aeruginosa (gram-negative) drug-resistant strain and P. vulgaris (gram-negative). The IC50 (µg/mL) of TR-1 was found to be most effective (15.70 ± 1.3 µg/mL) compared to the reference drug acarbose (21.59 ± 1.5 µg/mL), hence, it was further selected for the kinetic studies in order to illustrate the mechanism of inhibition. The enzyme inhibitory kinetics and mode of binding for the most active inhibitor (TR-1) was performed which showed that the compound is a non-competitive inhibitor and effectively inhibits the target enzyme by binding to its binuclear active site reversibly.

Pyridine Scaffolds, Phenols and Derivatives of Azo Moiety: Current Therapeutic Perspectives.

Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure-activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years.

Potential risk assessment of miR-143 gene polymorphisms rs41291957 and rs353292 in colorectal cancer.

Colorectal cancer is a life-threatening and therapeutically challenging disease. Increasingly it is being deciphered that genetic and epigenetic mutations play a central role in cancer onset and progression. Excitingly, discovery of non-coding RNAs is considered to be a milestone in molecular oncology and emerging evidence is deepening our understanding about pivotal role of miRNAs in carcinogenesis. miR-143 has been experimentally verified to play an instrumental role as tumor suppressor. Recent studies suggest that single nucleotide polymorphisms rs41291957 and rs353292 in miR-143 may associate with the progression and or development of colorectal cancer. In present study 400 Pakistani subjects participated including 200 colorectal cancer patients and 200 age and gender matched healthy individuals. Blood samples and clinical information of the confirmed patients was collected from cancer diagnosis and treatment hospitals in Pakistan. The polymorphisms rs41291957 and rs353292 were genotyped in patients and controls by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and results were validated by Sanger sequencing. The association of the SNPs within the study group was analyzed by χ² test with p value < 0.05 as significant. Odds ratio was calculated with 95% confidence interval.Genetic predisposition to cancer was observed in presence of characteristic rs45291957 polymorphism. χ² test results show strongly significant association mi-RNA rs45291957 SNP with colorectal cancer p value 0.0111 (<0.05) along with the statistically significant correlation tested by odds ratio with 95% confidence interval. However, no significant correlation (p value 0.6683) could be found for the association of rs353292 with colorectal cancer in Pakistani population. The present study for the first time gave evidence of miR-143 rs41291957 involvement in colorectal cancer patients of Pakistani population. This target can be a useful molecular tool for the prognosis and treatment targets for colorectal cancer in Pakistani population. rs353292 genetic association can be explored for different cancers in Pakistan to completely rule out its role in cancer.

Molecular Docking, Synthesis, and Tyrosinase Inhibition Activity of Acetophenone Amide: Potential Inhibitor of Melanogenesis.

Tyrosinase and its related proteins are responsible for pigmentation disorders, and inhibiting tyrosinase is an established strategy to treat hyperpigmentation. The carbonyl scaffolds can be effective inhibitors of tyrosinase activity, and the fact that both benzoic and cinnamic acids are safe natural substances with such a scaffolded structure, it was speculated that hydroxyl-substituted benzoic and cinnamic acid derivatives may exhibit potent tyrosinase inhibitory activity. These moieties were incorporated into new chemotypes that displayed in vitro inhibitory effect against mushroom tyrosinase with a view to explore antimelanogenic ingredients. The most active compound, 2-((3-acetylphenyl)amino)-2-oxoethyl(E)-3-(2,4-dihydroxyphenyl)acrylate (5c), inhibited mushroom tyrosinase with an IC50 of 0.0020 ± 0.0002 µM, while 2-((3-acetylphenyl)amino)-2-oxoethyl 2,4-dihydroxybenzoate (3c) had an IC50 of 27.35 ± 3.6 µM in comparison to the positive control arbutin and kojic acid with a tyrosinase inhibitory activity of IC50 of 191.17 ± 5.5 µM and IC50 of 16.69 ± 2.8 µM, respectively. Analysis of enzyme kinetics revealed that 5c is a competitive and reversible inhibitor with dissociation constant (Ki) value 0.0072 µM. In silico docking studies with mushroom tyrosinase (PDB ID 2Y9X) predicted possible binding modes in the enzymatic pocket for these compounds. The orthohydroxyl of the cinnamic acid moiety of 5c is predicted to form hydrogen bond with the active site side chain carbonyl of Asn 260 (2.16 Å) closer to the catalytic site Cu ions. The acetyl carbonyl is picking up another hydrogen bond with Asn 81 (1.90 Å). The inhibitor 5c passed the panassay interference (PAINS) alerts. This study presents the potential of hydroxyl-substituted benzoic and cinnamic acids and could be beneficial for various cosmetic formulations.

Medicinal Importance of Azo and Hippuric Acid Derivatives.

In this review, specific therapeutic and medicinal advantages including antiviral, antibacterial, antifungal and antitumor, strategies for drug designing, structure-activity relationship, advances in the syntheses of azo and hippuric acid derivatives of more than 50 compounds have been discussed since 2009-2018. It is found that phenyl-diazenyl azo derivatives and pyridinyl substituted hippuric acid derivatives showed promising antiretroviral potential. The incorporation of azo functionality to the respective quinolones and coumarin moieties and the insertion of thiocarbazone to hippuric acid displayed immense antibacterial activities. While, azo and hippuric acid derivatives of triazole and phenyl species gave maximum fungicidal as well as cytotoxic activities.

Physical Activity and Depression Among Young Adults in Islamabad: A Cross-sectional Study.

Objective To determine the relationship between physical activity and depression between the two genders amongst the young adults of Islamabad. Methods We conducted a cross-sectional study of students who were studying in various colleges and universities of Islamabad. Students who were willing to participate in the study and who were studying in the institute for more than six months were included in the study. The data was collected through a self-reporting questionnaire and a self-constructed questionnaire. Cronbach's alpha was used to assess the internal consistency of the self-constructed questionnaire, and it was found to be 0.69. The data obtained were analyzed on IBM's Statistical Package for the Social Sciences (SPSS) version 21 (IBM, Armonk, NY, US). Results Out of 298 participants, 113 (38%) were males and 185 (62%) were females. The mean age of the participants was 21.60±1.39 years. One-hundred twenty-six participants were found most likely to suffer from depression. Out of these 126 participants, 42 (33%) were females and 84 (67%) were males. Thirty-nine percent of the participants reported fatigue and inability to attend to their normal routine. Pearson correlation was calculated for the association of depression and age, and it was found to be significant (p-value less than 0.05). The correlation for depression with respect to physical activity was also found to be significant (p-value less than 0.05). Conclusions Low levels of physical activity can be a major risk factor for the development of depression and the possible exacerbation of any pre-existing mental disorder. There is a need to combat this problem to decrease the use of pharmaceutical means for curing depression.