"In-silico Design and Development of Novel Hydroxyurea Lipid Drug Conjugates for Breast Cancer Therapy Targeting PI3K/AKT/mTOR Pathway".

Hydroxyurea (HU) has shown promise in breast cancer treatment, but its hydrophilic nature limits its efficacy. Therefore, conjugating HU with lipids could increase its liphophilicity and improve its cellular uptake, leading to increased efficacy and reduced toxicity. The PI3K/Akt/mTOR pathway is an attractive therapeutic target in cancer not only because it is the second most frequently altered pathway after p53, but also because it serves as a convergence point for many stimuli. The aim of this study is to design and develop novel hydroxyurea lipid drug conjugates for breast cancer therapy targeting the PI3K/Akt/mTOR pathway using in-silico and in-vitro approaches. The conjugates are designed and docked with the proteins selected for each target like PI3K (PDB ID;2JDO), AKT (PDB ID;3APF), mTOR (PDB ID;4JST). The conjugates with higher docking scores are taken for ADME studies and molecular dynamics. Stearic, lauric, palmitic, myristic and linolenic acids have been used for the conjugation. The conjugates are synthesized and characterized. The HLB calculation and partition coefficient are carried out to find the improvement in liphophilicity of the conjugates compared to hydroxyurea. Finally, the in-vitro cytotoxicity studies are performed with MCF -7 cell lines and the compound HU-MA (hydroxyurea with myristic acid) with low IC50 is considered as the compound having good activity with compound code. These conjugates have been shown to have improved drug solubility and better cellular uptake compared to free hydroxyurea, which can increase drug efficacy.

A Descriptive Study of Atherogenic Indices in Patients Admitted to a Tertiary Care Hospital.

Introduction Atherogenic indices, as common factors implicated in the pathogeneses of atherogenic dyslipidemias and cardiometabolic disorders, provide inexpensive and less invasive aids for assessing the prognosis of hospitalized patients. Hence, we evaluate the atherogenic index profiles of patients admitted to a tertiary care hospital and correlate them with comorbidities, statin use, and duration of hospital stay. Methodology This cross-sectional study included 412 hospitalized patients aged >18 years undergoing lipid profiling, irrespective of their diagnosis. Their atherogenic indices were calculated from their lipid profile parameters and correlated with their comorbidities, statin use, and duration of hospital stay. Statistical analysis was done using the Mann-Whitney U test and Spearman's rank correlation coefficient tests, with a p-value of <0.05 indicating statistical significance. Results The participating cohort showed a mean age of 56.01±13.32 years. Nearly 63.0% of these had diabetes mellitus, 52.0% had hypertension, 34.0% had coronary artery disease, 16.0% had a cardiovascular accident, and 16.5% reported statin use. There was no significant difference in the distribution of any of the atherogenic indices over any of the comorbidities like diabetes mellitus, hypertension, coronary artery disease, or statin use, except for the non-high-density lipoprotein cholesterol distribution, which was significantly associated with coronary artery disease (p-value = 0.0112) and statin use (p-value = 0.0057). Atherogenic indices were not correlated with the duration of hospital stay (p-value > 0.05). Discussion This study suggests that non-high-density lipoprotein cholesterol may serve as an indicator of coronary artery disease and statin use. However, other atherogenic indices may not serve as reliable predictors of the duration of a hospital stay.