In recent years, N-Myristoyltransferase (NMT) has been identified as a new target for the treatment of fungal infections. It is observed that at present, there are increased rates of morbidity and mortality due to fungal infections. Hence, a series of novel myristic acid derivatives were designed via molecular docking studies and ADMET studies by targeting NMT (N-Myristoyltransferase). The designed myristic acid derivatives were synthesized by converting myristic acid into myristoyl chloride and coupling it with aryl amines to yield corresponding myristic acid derivatives. The compounds were purified and characterized via FTIR, NMR and HRMS spectral analyses. In this study, we carried out a target NMT inhibition assay. In the NMT screening assay results, the compounds 3u, 3m and 3t showed better inhibition compared to the other myristic acid derivatives. In an in vitro antifungal evaluation, the myristic acid derivatives were assessed against Candida albicans and Aspergillus niger strains by determining their minimal inhibitory concentrations (MIC₅₀). The compounds 3u, 3k, 3r and 3t displayed superior antifungal capabilities against Candida albicans, and the compounds 3u, 3m and 3r displayed superior antifungal capabilities against Aspergillus niger compared to the standard drug FLZ (fluconazole). Altogether, we identified a new series of antifungal agents.

Despite the availability of human papillomavirus (HPV) vaccines and screening facilities at various health centers in Saudi Arabia, the annual death rate due to cervical cancer is high. Therefore, knowledge and awareness are essential for self-care and educating others, particularly among healthcare students. The present descriptive, cross-sectional study explored female pharmacy students’ knowledge, attitudes, and practices related to cervical cancer. A total of 140 students participated in the survey. The survey was conducted for the period between April 2022 to September 2023. We observed a good knowledge score and positive attitudes among 8.5% and 93.5% of participants, respectively. A total of 10% of the study participants reported good practice scores. Most participants had never been screened for cervical cancer (94.3%). Among the non-screened subjects, feeling healthy and lacking information were the participants’ significant reasons for not screening for cervical cancer. A positive history of cancer related to smoking significantly impacted the knowledge score (p = 0.050). The current study reveals that healthcare awareness programs for cervical cancer and HPV vaccination are necessary at the level of educational institutions to improve public health.

Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using N-alkyl-1H-indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60–65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives 4c and 4d displayed very good cytotoxic activity, with IC₅₀ values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.

CDK4/6 and aromatase are prominent targets for breast cancer drug discovery and are involved in abnormal cell proliferation and growth. Although aromatase inhibitors have proven to be effective (for example exemestane, anastrozole, letrozole), resistance to treatment eventually occurs through the activation of alternative signaling pathways, thus evading the antiproliferative effects of aromatase inhibitors. One of the evasion pathways is Cylin D-CDK4/6-Rb signaling that promotes tumor proliferation and resistance to aromatase inhibitors. There is significant evidence that the sequential inhibition of both proteins provides therapeutic benefits over the inhibition of one target. The basis of this study objective is the identification of molecules that are likely to inhibit both CDK4/6 and aromatase by computational chemistry techniques, which need further biochemical studies to confirm. Initially, a structure-based pharmacophore model was constructed for each target to screen the sc-PDB database. Consequently, pharmacophore screening and molecular docking were performed to evaluate the potential lead candidates that effectively mapped both of the target pharmacophore models. Considering abemaciclib (CDK4/6 inhibitor) and exemestane (aromatase inhibitor) as reference drugs, four potential virtual hit candidates (1, 2, 3, and 4) were selected based on their fit values and binding interaction after screening a sc-PDB database. Further, molecular dynamics simulation studies solidify the stability of the lead candidate complexes. In addition, ADMET and DFT calculations bolster the lead candidates. Hence, these combined computational approaches will provide a better therapeutic potential for developing CDK4/6-aromatase dual inhibitors for HR+ breast cancer therapy.

Background/Objectives: Nilotinib (NTB) a tyrosine kinase inhibitor, helps CML patients with the Philadelphia chromosome. An increasingly rigorous dose regimen and a boxed warning limit the drug's use. NTB should be taken orally on an empty stomach two hours before and one hour after the dosage. A new reduced-dose nanoparticle formulation of NTB reduces the effect of food on PK and achieves equivalent bioavailability (BA) while fasting. The study investigated if nanostructured lipid carriers could make BCS class II medication NTB more soluble and easier to swallow. Methods: The formulation was optimized using the "Box-Behnken design (3-factor, 3-level)". Polydispersity index, Zeta potential, EE, and particle size were dependent variables, while total lipid concentration, surfactant concentration, and sonication time were independent. Investigation of the optimized formulation's in vivo pharmacokinetics, tissue absorption, and in vitro release. Results: In the optimized formulation, PDI, particle size, EE%, and ZP were 135.26±3.86 nm, 0.126±0.09, 89.62±1.26%, and -42.16±1.75mV, respectively. Transmission electron microscopy revealed circular particles. In vitro, NTB released 96.15% with pure NTB dispersion and 56.34% with NTB-NLCs after 24 hours. The data was acquired using a zero order. NTB was ad-ministered to acute myeloid, acute lymphoblastic, and acute T cell leukaemia at IC50 values of 251, 302, 398, 218, 248, and 225 µg/mL, respectively. NTB had IC50 values of 124, 118, 146, 125, 139, and 135 µg/mL against acute myeloid, acute lymphoblastic, and acute T cell leukaemia cell lines. Conclusions: The malignant leukaemia cell line's vitality decreased dose-dependently with NLCs and NTB. Our cytotoxicity experiments in various cell lines and Wistar rats enhanced oral bioavailability of NTB suggest that the optimized NTB-loaded NLCs.