Evaluation of fluorinated phospholipid analogs: A study on ADMET profiles, molecular docking and dynamics simulation
Saqib Ishaq1,2, Obaid Habib1, Abdul Aziz2
1Guangdong Provincial Key Laboratory of System Biology and Synthetics Biology for Urogenital Tumors, School of Basic Medicine, Shenzhen University Medical School, Shenzhen University (SZU), Guangdong, China.
Abstract:
Fluorinated phospholipid analogs Edelfosine and Ilmofosine drug reveal expressive potential as antineoplastic factors though targeted interaction with heat shock protein (HSP70KDa1A), an essential mediator in cancer pathophysiology. Using evolved computational approaches, this research evaluated their ADMET (absorption, distribution, metabolism, excretion and toxicity) profiles receptor binding affinities and molecular dynamics. Molecular docking discernible vigorous interactions with Edelfosine drug displaying greater binding stability and consistent hydrogen bonding as confirmed by 100 ns molecular dynamics simulations. Comparative interpretation emphasized Edelfosine drug enhanced pharmacokinetic properties depicted by lower RMSD values, stable solvent-accessible surface area and reduced structural fluctuations relative to Ilmofosine drug. Functional annotation and phylogenetic investigation affirmed the evolutionary conservation and pivotal biological function of heat shock protein (HSP70KDa1A). These findings position Edelfosine drug as a promising candidate for targeted cancer therapy appropriated further experimental validation to elucidate its mechanisms of action and therapeutic efficacy.
Insights
Edelfosine and Ilmofosine show potential as cancer therapies by interacting with heat shock protein (HSP70KDa1A). Edelfosine demonstrated superior binding stability and pharmacokinetic properties in computational analyses, suggesting it as a promising targeted cancer treatment.
Area of Science:
- Oncology
- Computational Chemistry
- Biochemistry
Background:
- Fluorinated phospholipid analogs, Edelfosine and Ilmofosine, are investigated for their antineoplastic properties.
- Heat shock protein (HSP70KDa1A) is a key mediator in cancer pathophysiology and a potential therapeutic target.
Purpose of the Study:
- To evaluate the absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles, receptor binding affinities, and molecular dynamics of Edelfosine and Ilmofosine.
- To compare the computational profiles of Edelfosine and Ilmofosine for their potential as targeted cancer therapeutics.
Main Methods:
- Computational approaches including molecular docking and 100 ns molecular dynamics simulations were employed.
- Analysis of ADMET profiles, receptor binding affinities, and molecular dynamics was performed.
- Functional annotation and phylogenetic investigation of HSP70KDa1A were conducted.
Main Results:
- Edelfosine exhibited vigorous interactions with HSP70KDa1A, displaying greater binding stability and consistent hydrogen bonding compared to Ilmofosine.
- Molecular dynamics simulations confirmed Edelfosine's enhanced pharmacokinetic properties, indicated by lower RMSD values and stable solvent-accessible surface area.
- Phylogenetic analysis confirmed the evolutionary conservation and critical biological role of HSP70KDa1A.
Conclusions:
- Edelfosine demonstrates superior binding stability and pharmacokinetic advantages over Ilmofosine.
- Edelfosine is a promising candidate for targeted cancer therapy, warranting further experimental validation.
- The study highlights the significance of HSP70KDa1A as a therapeutic target in cancer treatment.
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