Background

The ADMET profiles of chlorinated phospholipid analogs, including miltefosine and perifosine, have been extensively studied for their potential as antineoplastic agents. ADMET evaluations can provide insight into the pharmacokinetic and pharmacodynamic properties of a compound, as well as its safety and efficacy in vivo. Studies have shown that these compounds have promising antineoplastic activity, and their ADMET profiles have provided valuable information for further evaluation in clinical trials.

Material & Methods:

The present study aims to identify drugs with similar and dissimilar ADMET profiles to these compounds, investigate their activity against normal and tumor cell lines, and study their interaction with heat shock protein 90 (HSP90) using molecular docking. The target with the active binding site drug molecule is identified using a 1-click docking server.Binding Property Explorer was employed to determine drug-likeness, and the admetSARprogramme was used to determine ADMET analysis. CLC-Pred was used to retrieve the impact of chlorinated these drugs on both normal and tumour cell lines. All of these drugs were isolated from CLC-Pred to determine their toxicity.

Results:

In admet properties, total 30 SMILEs were extracted from chemdraw after were chlorinated. Several transporters have been demonstrated to regulate some medicines' actions, which impacts their ADMET characteristics. All of these drugs were isolated from CLC-Pred to determine their toxicity. Such toxicity are summarized as Breast adenocarcinoma, Lung carcinoma, Prostate carcinoma, Gastric carcinoma, colon adenocarcinoma, non small cell lung carcinoma, Uterina corpus sacoma and Papillary renal carcinoma. The heat shock protein 90alpha 3D model was generated from the PDB and 1-click docking server. Comparing two drugs ligand to find their analogous and dissimilar ADMET characteristics (miltefosine, perifosine). These drug molecules select on the basis of molecular weight. The molecular weight and molecular formula of miltefosine is (407.6, C₂₁H₄₆NO₄P) and perifosine (461.7, C₂₅H₅₂NO₄P). Comparative docking results of 30 compounds of these drug molecules by 1- Click docking are listed in Table 1. Heat shock protein 90Alpha interacts with all 30 chlorinated drug compounds.

Discussion: Miltefosine and perifosine are alkylphosphocholine compound that have been utilized used as anti-cancer drugs. Miltefosine has demonstrated promising results against various malignancies include ovarian, breast and prostate cancers for the treatment of visceral leishmaniasis. Whereas periforosine is a strong Akt inhibitor that has been examined in clinical studies for a variety of cancer types. The metabolic stability, lipophilicity and cytotoxicity of medicines have all been found to be improved by this alteration. Miltefosine, an FDA-approved medication for the treatment of leishmaniasis, is a derivative known as chlorinated Miltefosine. Perifosine, on the other hand, is a synthetic alkylphospholipid that has demonstrated potential in preclinical studies as an antineoplastic drug.

Conclusion:In conclusion, Miltefosine and perifosine's cytotoxicity, metabolic stability, and anticancer activity were found to be improved by chlorination both in vitro and in vivo. These results suggest that perifosine and miltefosine, which are chlorinated, may be potential candidates for the development of new anticancer drugs. To further analysis these compounds work needed their safety and effectiveness in clinical trials.

Keywords: Admet properties, Toxicity, Admetsar, CLC-Pred, Molecular Docking