Elucidating the structural basis for the enhanced antifungal activity of amide derivative against Candida albicans: a comprehensive computational investigation.

The continuous search for more effective options against well-known pathogens such as Candida albicans remains the rationale for the search for novel lead compounds from various sources. This study aims to investigate the chemical structure, chemical properties, of 5-(2-((5-(((1S,3R) -3-(5-acetamido-1,3,4-thiadiazolidin-2-yl) cyclopentyl) methyl)-1,3,4-thiadiazolidin-2-yl)amino)-2-oxoethyl)-2-methyl-2,3-dihydro-1H-pyrazol-3-ide designated ATCTP using DFT method ωB97XD/-311 + + g(2d, 2p) and the biological potential of compound ATCTP against Candida albicans using molecular docking and ADMET studies. Geometry optimization was carried out in DMSO, ethanol. gas and water revealing minute discrepancies in bond length and wider differences in bond angles. Frontier molecular orbital investigations reveal HOMO-LUMO energy gap magnitude in decreasing order of ATCTP_Gas > ATCTP_Water > ATCTP_ethanol > ATCTP_DMSO inferring that water influences chemical stability of the compound the most compared to ethanol and DMSO. Density of state investigations have revealed electron density contributions at corresponding energy peaks. In silico pharmacokinetic predicts ATCTP not to be cytotoxic, hepatotoxic, immunotoxic or mutagenic but probable mutagen. Molecular docking investigation of ATCTP against aspartic proteinase of Candida albicans (ID: 2QZX) in comparison with standard drug Fluconazole. Compound ATCTP had higher binding affinity (- 8.1 kcal/mol) compared to that of the standard drug fluconazole (- 5.6 kcal/mol) which records 4 conventional hydrogen interactions compared to 2 formed in the interaction of ATCTP + 2QZX. ATCTP also reports binding affinity of - 7.2 kcal/mol which reportedly surpassed that of 2QZX interaction with fluconazole (- 5.7 kcal/mol). ATCTP binds with lanosterol14-α-demethylase (5v5z) with binding affinity of - 9.7 kcal/mol binding to active site amino acid residues of the protein compared to fluconazole + 5v5z (- 8.0 kcal/mol). ATCTP is therefore recommended to be a lead compound for the possible design of a new and more effective anti-candida therapeutic compound.

Systematic exo-endo encapsulation of hydroxyurea (HU) by Cu, Ag, and Au-doped gallium nitride nanotubes (GaNNT) for smart therapeutic delivery.

Similar to the more well-known carbon nanotubes, gallium nitride nanotubes (GaNNT) are among the materials that scientists have found to be extremely helpful in transporting drugs and to provide significant potential for multi-modal medical therapies. Here, the potential of Cu, Ag, and Au-doped GaNNT for smart delivery of the anticancer medication hydroxyurea (HU) was extensively investigated employing quantum chemical analysis and density functional theory (DFT) computation at the B3LYP-GD3BJ/def2-SVP level of theory. The systematic approach used in this study entails examining the exo (outside)-and endo (inside) loading of HU utilizing the investigated nanotubes in order to understand the adsorption, sensing processes, bonding types, and thermodynamic properties. Results of the HOMO-LUMO studies show that metal-doped GaNNTs with the hydroxyurea (HU) at the endo - interaction of the drug of the nanotube produced more reduced energy gaps (0.911-2.039 eV) compared with metal-doped GaNNTs complexes at the outside - interaction of the drug on the nanotube (2.25-3.22 eV) and as such reveal their suitability for use as drug delivery materials. As observed in the endo-interaction of HU adsorptions in the tubes, HU_endo_Au@GaNNT possessed the highest adsorption energy values of -118.716 kcal/mol which shows the most chemisorption between the surfaces and the adsorbate while for HU_exo_Ag@GaNNT is -97.431 kcal/mol for the highest exo-interactions. These results suggest that HU drug interacted inside the Ag, Au, and Cu doped GaNNT will be very proficient as a carrier of the HU drug into bio systems. These results are along with visual studies of weak interactions, thermodynamics, sensor, and drug release mechanisms suggest strongly the endo-encapsulation of HU as the best mode for smart drug delivery.

Circulation of hepatitis B virus genotype-E among outpatients in tertiary hospitals in the Niger-Delta region of Nigeria.

Introduction: Hepatitis B virus (HBV) infection continues to be a significant public health challenge globally, with higher disease burden in developing countries. HBV genotypes are associated with different geographical regions and clinical outcomes. Limited information exists on epidemiology of HBV in the Niger-Delta region (South-South) of Nigeria. Consequently, this study was designed to characterise hepatitis B virus infection among outpatients in selected tertiary hospitals in the region. Methodology: Between June and August 2017, consenting nine hundred asymptomatic out-patients were enrolled and initially screened for HBV infection using one step Hepatitis B surface antigen (HBsAg) strip and subsequently re-tested using HBsAg and Hepatitis B core total antibody (anti-HBc) specific Enzyme-Linked Immunosorbent Assay (ELISA). Blood serum with detectable HBsAg were subsequently subjected to DNA extraction, S-gene amplification using a nested polymerase chain reaction (PCR) protocol, gel electrophoresis, sequencing and phylogenetic analysis. Results: Seroprevalence of HBsAg was 4.6% (95% CI 2.5-7.1) and anti-HBc was 10.1% (95% confidence interval (CI) 6.1-15.3). Of the 41 HBsAg positive samples subjected to DNA extraction and HBV S-gene specific PCR, only 6 (14.6%) yielded the expected ∼408bp band. Phylogenetic analysis based on HBV pre-S/S sequences identified all six typable samples as genotype E, subtype ayw4 of the West African clade. Conclusion: Results of the study confirm the presence and circulation of HBV genotype-E in the Niger-Delta region of Nigeria, thus corroborating the inclusion of the country in the Genotype E crescent. The authors advocate value-added HBV intervention in the region and the country at large.