title: Molecular docking of the anticancer bioactive compound proceraside with macromolecules involved in the cell cycle and DNA replication.
abstract: The bioactive compounds proceraside A, frugoside and calotropin, which were extracted from the root bark of Calotropis procera (Aiton) W.T. Aiton (family Asclepiadaceae), were recently reported to inhibit the growth of inhibition against various human cancer cell lines in vitro. However, their modes of action have not been clearly defined. Therefore, we attempted an in silico approach to gain insights into their binding modes against the following selected molecular targets: CDK-2, CDK-6, topoisomerase I, BCL-2, VEGFR-2, telomere: G-quadruplex, and topoisomerase II. These targets were selected based on their key roles in cancer progression via the regulation of the cell cycle and DNA replication. Molecular-docking analyses revealed that proceraside A was the best docked ligand against all the targets, with the exception of telomere-G: quadruplex. Furthermore, it displayed the lowest binding energies and inhibition constants, and critical hydrogen bonds and hydrophobic interactions with the targets were also revealed. The present study may aid in the identification of possible targets for proceraside A, and might provide a plausible explanation for its proven anti-tumor activities. Moreover, the result of this study may further guide structure-activity relationship studies used to generate more potent target-specific inhibitors.
authors.affiliation: Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong, Meghalaya, India.
authors.forename: A B
authors.initials: AB
authors.lastname: Gurung
authors.affiliation: Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: M A
authors.initials: MA
authors.lastname: Ali
authors.affiliation: Department of Biotechnology and Bioinformatics, North Eastern Hill University, Shillong, Meghalaya, India.
authors.forename: A
authors.initials: A
authors.lastname: Bhattacharjee
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: AbulFarah
authors.affiliation: Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: F
authors.initials: F
authors.lastname: Al-Hemaid
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: F M
authors.initials: FM
authors.lastname: Abou-Tarboush
authors.affiliation: Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: K M
authors.initials: KM
authors.lastname: Al-Anazi
authors.affiliation: Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.
authors.forename: F S M
authors.initials: FS
authors.lastname: Al-Anazi
authors.affiliation: Department of Environment and Forest Resources, Chungnam National University, Yuseong-gu, Daejeon, Republic of Korea.
authors.forename: J
authors.initials: J
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D002298:Cardenolides / Q000737:chemistry / Q000494:pharmacology; D002301:Cardiac Glycosides / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000502:physiology; D045744:Cell Line, Tumor; D004261:DNA Replication / Q000502:physiology*; D004073:Digitoxigenin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances / Q000737:chemistry* / Q000378:metabolism; D062105:Molecular Docking Simulation; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002298:Cardenolides; D002301:Cardiac Glycosides; D008024:Ligands; D046911:Macromolecular Substances; C000593283:proceraside A; D004073:Digitoxigenin; C546414:calotropin; C025778:cannogenol-3-O-beta-D-allomethyloside