“In-silico Design and Development of Novel Hydroxyurea Lipid Drug Conjugates for Breast Cancer Therapy Targeting PI3K/AKT/mTOR Pathway”
Drug Res (Stuttg) 2024; 74: 32-41 DOI: 10.1055/a-2213-8457Hydroxyurea (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 -...
Source: Drug Research - Category: Drugs & Pharmacology Authors: Dharmaraj, Saranya Swaroop, Akey Krishna Esakkimuthukumar, Mariappan Negi, Preeya Jubie, Selvaraj Tags: Original Article Source Type: research
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