Please use this identifier to cite or link to this item: http://hdl.handle.net/10995/103279
Title: Synthesis of novel cytotoxic tetracyclic acridone derivatives and study of their molecular docking, ADMET, QSAR, bioactivity and protein binding properties
Authors: Veligeti, R.
Madhu, R. B.
Anireddy, J.
Pasupuleti, V. R.
Avula, V. K. R.
Ethiraj, K. S.
Uppalanchi, S.
Kasturi, S.
Perumal, Y.
Anantaraju, H. S.
Polkam, N.
Guda, M. R.
Vallela, S.
Zyryanov, G. V.
Зырянов, Г. В.
Issue Date: 2020
Publisher: Nature Research
Citation: Synthesis of novel cytotoxic tetracyclic acridone derivatives and study of their molecular docking, ADMET, QSAR, bioactivity and protein binding properties / R. Veligeti, R. B. Madhu, J. Anireddy, et al. — DOI 10.1038/s41598-020-77590-1 // Scientific Reports. — 2020. — Vol. 10. — Iss. 1. — 20720.
Abstract: Acridone based synthetic and natural products with inherent anticancer activity advancing the research and generating a large number of structurally diversified compounds. In this sequence we have designed, synthesized a series of tetracyclic acridones with amide framework viz., 3-(alkyloyl/ aryloyl/ heteroaryloyl/ heteroaryl)-2,3-dihydropyrazino[3,2,1-de]acridin-7(1H)-ones and screened for their in vitro anti-cancer activity. The in vitro study revealed that compounds with cyclopropyl-acetyl, benzoyl, p-hydroxybenzoyl, p-(trifluoromethyl)benzoyl, p-fluorobenzoyl, m-fluorobenzoyl, picolinoyl, 6-methylpicolinoyl and 3-nicotinoyl groups are active against HT29, MDAMB231 and HEK293T cancer cell lines. The molecular docking studies performed for them against 4N5Y, HT29 and 2VWD revealed the potential ligand–protein binding interactions among the neutral aminoacid of the enzymes and carbonyl groups of the title compounds with a binding energy ranging from − 8.1394 to − 6.9915 kcal/mol. In addition, the BSA protein binding assay performed for them has confirmed their interaction with target proteins through strong binding to BSA macromolecule. The additional studies like ADMET, QSAR, bioactivity scores, drug properties and toxicity risks ascertained them as newer drug candidates. This study had added a new collection of piperazino fused acridone derivatives to the existing array of other nitrogen heterocyclic fused acridone derivatives as anticancer agents. © 2020, The Author(s).
Keywords: ACRIDONE
ACRIDONE DERIVATIVE
ANTINEOPLASTIC AGENT
PROTEIN BINDING
CELL LINE
CHEMISTRY
DRUG SCREENING
HEK293 CELL LINE
HT-29 CELL LINE
HUMAN
MOLECULAR DOCKING
PHYSIOLOGY
PROCEDURES
QUANTITATIVE STRUCTURE ACTIVITY RELATION
TUMOR CELL LINE
ACRIDONES
ANTINEOPLASTIC AGENTS
CELL LINE
CELL LINE, TUMOR
DRUG SCREENING ASSAYS, ANTITUMOR
HEK293 CELLS
HT29 CELLS
HUMANS
MOLECULAR DOCKING SIMULATION
PROTEIN BINDING
QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP
URI: http://hdl.handle.net/10995/103279
Access: info:eu-repo/semantics/openAccess
SCOPUS ID: 85096694388
PURE ID: 20221269
2bf574cb-697a-4390-b5de-f3982d171a07
ISSN: 20452322
DOI: 10.1038/s41598-020-77590-1
metadata.dc.description.sponsorship: The authors thank GVK Biosciences Pvt. Ltd., Nacharam, Hyderabad, India for sponsoring chemicals and analytical data. Authors Dr. Avula Vijaya Kumar Reddy and Prof. Dr. Grigory V. Zyryanov thank Ural Federal University for support and acknowledge the financial support of the Russian Science Foundation, Moscow, Russian Federation (RSF Grant No.: 18-13-00365). The corresponding author Dr. Visweswara Rao Pasupuleti thank Universiti Malaysia Sabah for the financial support.
RSCF project card: 18-13-00365
Appears in Collections:Научные публикации, проиндексированные в SCOPUS и WoS CC

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