Analysis of Novel C-X-C Chemokine Receptor Type 4 (CXCR4) Inhibitors from Hexane Extract of Euclea crispa (Thunb.) Leaves by Chemical Fingerprint Identification and Molecular Docking Analysis

Abstract

Objectives: To evaluate the potential inhibitors aginst CXCR4 from hexane extract of Euclea crispa (E. crispa) leaves. Methods: The natural compounds were identified and charecterized through GC-MS Analysis. Molecular docking studies carried out to investigatethe inhibitory activity angainst CXCR4. Absorption, Distribution, Metabolism, and Excretion (ADME) properties also were predicted to find pharmacokinetics and pharmacodynamics of compounds.Results:The molecular docking simulations revealed that, Benzoic acid 3-methyl-4-(1,3,3,3-tetrafluoro-2-methoxycarbonyl-propenylsulfanyl)-phenyl ester (SCHEMBL15979821), Hydrocortisone Acetate and Phenyl Glucuronide possess good inhibitory activites (Glide Score of -7.06, -6.97, -6.47 and Glide Energy of -43.22, -48.27 and -32.80 kcal/mol respectively) when compared with standard FDA approved drug and other compounds. All the screened compounds were within the acceptable and permissible limits of ADME properties. Conclusion: Thus, from this study it can be concluded that, these screened natural compounds from E. crispa leaves may serve as potential inhibitors for CXCR4 and they might lead to development of new therapeutic agents against cancer and its associated complications.Key words: E.crispa, GC-MS analysis, CXCR4, Molecular docking, ADME properties. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. Correspondence

[Retracted] (5E,7E)‐4,5,6 Trihydroxy‐3‐(hydroxymethyl)tetrahydro‐2H‐pyran‐2‐ylheptadeca‐5,7‐dienoate from Euclea crispa (L.) Inhibits Ovarian Cancer Cell Growth by Controlling Apoptotic and Metastatic Signaling Mechanisms

“…Nevertheless, the chemopreventive potential of the plant extract and isolated compound 2 in in vitro human cell line model has been reported. Hence, this study analyzed the cytotoxic, antiproliferative, and antiapoptotic potential of the isolated compound 2 in a human ovarian cancer cell line (HO-8910) [ 6 , 15 ]. To assess the cytotoxicity of compound 2 on the increased growth of ovarian cancer cells, HO-8910 cells were treated with different concentrations of the compound (10, 20, 30, 40, 50, and 60 μ g) and the cell capability was identified by the MTT method.…”

“…It contributes to activating its downstream signaling cascades, which could facilitate tumour cell proliferation, metastasis, and angiogenesis [ 44 , 45 ]. The overexpression of this oncogene performs a mandatory function in the growth and progress of cancer cells, and it acts as novel therapeutic target sites for ovarian and breast cancer [ 6 ]. In this study, compound treatment to HO-8910 cells expressed a substantial decrease in HER2 protein expression compared with the control cells ( Figure 9(b) ) and a subsequent substantial reduction ( p < 0.05) in the Akt protein level ( Figure 9(c) ), suggesting that compound 2 inhibits chemokines and epidermal growth factor receptor-mediated cell proliferation and metastasis in HO-8910 cells.…”

“…Plants have a long history of use for the treatment of human diseases, particularly cancer, which is a lethal disease that causes deaths in individuals at a high rate [ 6 – 8 ]. Several medicinal plants have been reported to exhibit a variety of pharmacological and/or life functions such as antioxidant, antimicrobial, anti-inflammatory, anticancer, and antidiabetic, due to the presence of some active phytocompounds and compounds that possess aromatic hydroxylated rings [ 9 – 11 ].…”

“…The fruits are edible. The antioxidant activity of E. crispa leaves is investigated using the ethanolic extracts of the leaves by isolating the bioactive compounds [ 6 , 20 ]. Thus, the bioactive compounds are isolated as an initiative to also extend the horizon to predict the chemotherapeutic activities of the plant to benefit mankind.…”

Characterization of (2E,6E)-3,7,11-Trimethyldodeca-2,6,10-Trien-1-Ol with Antioxidant and Antimicrobial Potentials from <i>Euclea Crispa</i> (Thunb.) Leaves

“…Powdered material of E. crispa leaves was extracted by the method of exhaustive extraction [17]. Briefly,400g of the plant leaf powder was soaked in 2000 mL of ethanol contained flask and it was kept on the rotating shaker for 72 hours at 25 o C (average room temperature).…”