Computational drug repurposing effort for identifying novel hits for the treatment of diseases such as endometriosis, uterine fibroids, and prostate cancer.

This research aimed to identify potential drug compounds from the ZINC15 molecule database that could effectively treat GnRH1R-related diseases. The study utilized molecular docking and molecular dynamics methods to achieve this goal, which is crucial in drug repurposing research. The virtual screening process involved analyzing known drug compounds using molecular docking. Additionally, molecular dynamics simulations and MM-GBSA were employed to evaluate the stability of the complexes and determine the interactions between the compounds and protein structure. As a result, this study provides significant insights for treating diseases such as endometriosis, uterine fibroids, and prostate cancer related to GnRH1R. The study also involved designing new drugs and identifying necessary molecular scaffolds.

Synthesis, molecular modeling investigation, molecular dynamic and ADME prediction of some novel Mannich bases derived from 1,2,4-triazole, and assessment of their anticancer activity.

A series of biologically active novel Mannich bases containing with a 1H-1,2,4-triazole-5-one ring were developed to evaluate the cytotoxic activity. For this purpose, the synthesized Schiff Bases (S1-5) were reacted with formaldehyde and morpholine, which is a secondary amine to yield novel N-Mannich bases (M1-5) via the Mannich reaction. The structures of the compounds (M1-5) were determined structurally employing 1H/13C-NMR, IR and elemental analysis. In this study, we evaluated the cytotoxic potential of the compounds (M1-5) on the human hypopharyngeal carcinoma FaDu cells. We found that the compound (M3) possesses a significant anticancer feature against FaDu cells that might be evaluated with further in vitro and in vivo studies to understand its anticancer potential better. Lastly, comparisons were made using molecular docking calculations to find the theoretical activities of the compounds (M1-5). The docking score parameter of the compound (M3) against the 2DO4 protein is -5.67, the docking score parameter against the 5JPZ protein is -5.72, and finally, the docking score parameter against the 2H80 protein is -5.50. Molecular dynamic calculations are made for 0-100 ns. The ADME/T calculations were performed to find the drug potential of the compounds (M1-5). The results suggest that our drug candidate compound exhibits strong potential for co-administration with the antigen structures, owing to the low rate of interactions that decreased over time.Communicated by Ramaswamy H. Sarma.

Graphene quantum dots incorporated NiAl2O4 nanocomposite based molecularly imprinted electrochemical sensor for 5-hydroxymethyl furfural detection in coffee samples.

5-Hydroxymethyl furfural (HMF) is an intermediate produced by dehydrating sugars, such as fructose, sucrose, and glucose, in an acidic medium or during the Maillard reaction. It also occurs due to the storage of sugary foods at inappropriate temperatures. In addition, HMF is seen as a quality criterion in products. In this study, a novel molecularly imprinted electrochemical sensor based on graphene quantum dots incorporated NiAl2O4 (GQDs-NiAl2O4) nanocomposite was presented for the selective determination of HMF in coffee samples. Various microscopic, spectroscopic, and electrochemical methods were carried out for the structural characterizations of GQDs-NiAl2O4 nanocomposite. The molecularly imprinted sensor was prepared by multi-scanning using cyclic voltammetry (CV) in the presence of 100.0 mM pyrrole monomer and 25.0 mM HMF. After method optimization, the sensor revealed linearity towards HMF in the range of 1.0-10.0 ng L-1 with a detection limit (LOD) of 0.30 ng L-1. The developed MIP sensor's high repeatability, selectivity, stability, and fast response ability can provide reliable HMF detection in beverages, such as coffee, which is heavily consumed.

Synthesis and acetylcholinesterase enzyme inhibitory effects of some novel 4,5-Dihydro-1H-1,2,4-triazol-5-one derivatives; an in vitro and in silico study.

In this study, a series of novel Schiff bases (4a-4h) containing 1,2,4-triazole structure were synthesized through a condensation reaction of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones with 3-(4-methylbenzenesulfonyloxy)-benzaldehyde. The structures of 3-alkyl(aryl)-4-[3-(4-methylsulfonyloxy)-benzylidenamino]-4,5-dihydro-1H-1,2,4-triazol-5-ones (4a-h) were determined through a range of spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, and elemental analysis). In addition, enzyme inhibitory properties of the newly synthesized Schiff bases were determined against acetylcholinesterase (AChE). Their Ki values were calculated in the range of 0.70 ± 0.07-8.65 ± 5.6 µM. Besides, their IC50 values were calculated in the range of 0.43-3.87 µM. Finally, in silico molecular docking interactions of the compounds with AChE target enzyme (PDB ID:4EY7) were evaluated using Chimera and AutoDock Vina softwares. The lowest binding energy levels (-12.0 kcal/mol) of the compounds 4e and 4g with AChE target enzyme were verified the best binding affinities and molecular interactions.Communicated by Ramaswamy H. Sarma.

A novel sandwich-type SERS immunosensor for selective and sensitive carcinoembryonic antigen (CEA) detection.

Monitoring the malignant tumors via cancer biomarkers is very significant process. Nonetheless, the practical clinical applications need selective and sensitive analytical methods/techniques. In this study, a novel sandwich type immunosensor based on surface-enhanced raman scattering (SERS) was presented including 4-mercaptobenzoic acid labeled MoS2 nanoflowers@Au nanoparticles (MoS2 NFs@Au NPs/ MBA) as CEASERS tag and Fe3O4@Au nanoparticles functionalized delaminated Ti3C2Tx MXene (Fe3O4 NPs@Au NPs/d-Ti3C2TX MXene) as SERS magnetic supporting substrate for carcinoembryonic antigen (CEA) detection. Especially, the determination of single molecule by using SERS method enables early diagnosis of major diseases. In addition, this technique can be utilized for multiplex analyzes owing to narrow well-resolved peaks. The prepared CEASERS tag and SERS magnetic supporting substrate were characterized by scanning electron microscope (SEM), x-ray diffraction (XRD) method, x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and fourier transform infrared spectroscopy (FTIR). A linearity of 0.0001-100.0 ng mL-1 was observed with high sensitivity. Finally, sandwich type immunosensor demonstrated good selectivity and stability for target CEA recognition in plasma sample.

A novel and ultrasensitive sandwich-type electrochemical immunosensor based on delaminated MXene@AuNPs as signal amplification for prostate specific antigen (PSA) detection and immunosensor validation.

In this study, an ultra-sensitive electrochemical immunosensor for PSA detection was designed. Firstly, gold nanoparticles (AuNPs)/p-aminothiophenol (ATP) functionalized graphene oxide (GO) composite (AuNPs-ATPGO) was constructed and modified to glassy carbon electrode (AuNPs-ATPGO/GCE). AuNPs-ATPGO/GCE was utilized as immunosensor platform to increase the amount of PSA antibody1 (Ab1). After that, self-assembled delaminated MXene-gold nanoparticles (d-Ti3C2TX MXene@AuNPs) was used to label PSA seconder antibody2 (Ab2) as signal amplification. The prepared AuNPs-ATPGO, d-Ti3C2TX MXene@AuNPs and electrochemical immunosensor was charecterized by electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), scanning electron microscope (SEM), x-ray diffraction (XRD) method, x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FTIR). The linearity range and detection limit (LOD) were obtained as 0.01-1.0 pg mL-1 and 3.0 fg mL-1, respectively.