5-Oxo-dihydropyranopyran derivatives as anti-proliferative agents; synthesis, biological evaluation, molecular docking, MD simulation, DFT, and in-silico pharmacokinetic studies.

A series of ethyl 2-amino-7-methyl-5-oxo-4-phenyl-4,5-dihydropyrano[4,3-b]pyran-3-carboxylate derivatives (4a-j) bearing different substitutions on the C4-phenyl ring was synthesized. The anti-proliferative activity of all the synthesized compounds was assessed against two human cancer-cell lines, including SW-480 and MCF-7, by using MTT method. Derivatives 4g, 4i, and 4j, possessing 4-NO2, 4-Cl, and 3,4,5-(OCH3)3 substitutions, were found to be the most potent compounds against both cell lines. The obtained IC50 values for 4g, 4i, and 4j were 34.6, 35.9, and 38.6 µM against SW-480 cells and 42.6, 34.2, and 26.6 µM against MCF-7 cells, respectively. Evaluation of the free radical scavenging potential of the compounds against DPPH radicals showed the highest result for compound 4j with an EC50 value of 580 µM. Molecular docking studies revealed the compounds were well accommodated within the binding site of cyclin-dependent kinase-2 (CDK2) with binding energies comparable to those of DTQ (the co-crystallized inhibitor) and BMS-265246 (a well-known CDK2 inhibitor). Molecular dynamics simulation studies confirmed the interactions and stability of the 4g-CDK2 complex. All derivatives, except 4g, were predicted to comply with the drug-likeness rules. Compound 4j may be proposed as an anti-cancer lead candidate for further studies due to the promising findings from in-silico pharmacokinetic studies, such as high GI absorption, not being a P-gp substrate, and being a P-gp inhibitor. Density functional theory (DFT) analysis was performed at the B3LYP/6-311++G (d,p) level of theory to examine the reactivity or stability descriptors of 4d, 4g, 4i, and 4j derivatives. The highest value of energy gap between HOMO and LUMO and thermochemical parameters were obtained for 4i and 4j.

Factors Influencing the Effectiveness of E-Learning in Healthcare: A Fuzzy ANP Study.

E-learning has transformed the healthcare education system by providing healthcare professionals with training and development opportunities, regardless of their location. However, healthcare professionals in remote or rural areas face challenges such as limited access to educational resources, lack of reliable internet connectivity, geographical isolation, and limited availability of specialized training programs and instructors. These challenges hinder their access to e-learning opportunities and impede their professional development. To address this issue, a study was conducted to identify the factors that influence the effectiveness of e-learning in healthcare. A literature review was conducted, and two questionnaires were distributed to e-learning experts to assess primary variables and identify the most significant factor. The Fuzzy Analytic Network Process (Fuzzy ANP) was used to identify the importance of selected factors. The study found that success, satisfaction, availability, effectiveness, readability, and engagement are the main components ranked in order of importance. Success was identified as the most significant factor. The study results highlight the benefits of e-learning in healthcare, including increased accessibility, interactivity, flexibility, knowledge management, and cost efficiency. E-learning offers a solution to the challenges of professional development faced by healthcare professionals in remote or rural areas. The study provides insights into the factors that influence the effectiveness of e-learning in healthcare and can guide the development of future e-learning programs.