Molecular Docking, Drug Likeness, and ADMET Analyses of Passiflora Compounds as P-Glycoprotein (P-gp) Inhibitor for the
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CANCER CHEMOPREVENTION (R AGARWAL, CV RAO AND S YU, SECTION EDITORS)
Molecular Docking, Drug Likeness, and ADMET Analyses of Passiflora Compounds as P-Glycoprotein (P-gp) Inhibitor for the Treatment of Cancer Serap Yalcin 1 Accepted: 8 September 2020 # Springer Nature Switzerland AG 2020
Abstract Cancer disease leads to deaths worldwide. Anti-cancer drugs have a high prevalence of side effects and cause multidrug resistance (MDR) that remains a significant barrier to major cancer therapy. To date, chemical and herbal substances have been analyzed for their MDR modulatory activity. However, research on new and safe molecules has been continued to overcome MDR in cancer. The plant compounds can be an effective inhibitor for successful cancer therapy. Recently, computational models have gained importance to discover new inhibitors. In the present study, we aimed to explore the various compounds of Passiflora species as P-gp inhibitor. P-gp protein was docked with the active substrate and inhibitor, respectively, including tamoxifen and verapamil. Besides, 3D structure of Pgp was docked with 11 compounds (luteolin, beta amyrin, beta-sitosterol, chimaphilin, chrysin, edulan I and II, apigenin, oleanolic acid, stigmasterol, hydroxyflavone) of plant origin using AutoDock4.2 program. Furthermore, the compounds were analyzed for ADMET and drug likeness properties of compounds determined as Lipinski, Veber, and Ghose’s rules (http://www.swissadme.ch/). As obtained molecular docking analysis results, luteolin, chrysin, hydroxyflavone, and apigenin may be a candidate for being P-gp inhibitor. Hence, it may be of attention to consider these compounds for further in vitro and in vivo evaluation. Keywords P-gp inhibitor . Passiflora . Molecular docking . Drug likeness . ADMET
Introduction Traditional cancer therapies are surgery, radiation therapy, and chemotherapy, or their combinations [1]. Chemotherapy generally is more difficult important in the treatment of metastatic malignancies and it also causes multiple drug resistance (MDR) and side effects on healthy cells [2]. MDR demonstrates a large field of resistance against functionally and structurally unrelated chemotherapeutic agents [3, 4], is the ability of cancer cells to escape and to survive from chemotherapeutics in cancer therapy, and this situation seriously disrupts the success of cancer chemotherapy [4–7]. ATP-binding cassette transporters (ABC transporters) are a complicated pump superfamily, in which substrate is transported across membranes against a concentration gradient This article is part of the Topical Collection on Cancer Chemoprevention * Serap Yalcin [email protected] 1
Faculty of Sciences and Arts, Department of Molecular Biology and Genetics, Kırsehir Ahi Evran University, Kırsehir, Turkey
in the efflux of small molecule drugs [8–11]. P-glycoprotein (Pgp) is one of the well-described ABC transporters which are currently considered to be one of the important barriers in cancer therapy [12]. P-gp has an important role in drug resistance and it
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