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.
Highlights
Acridone based synthetic and natural products with inherent anticancer activity advancing the research and generating a large number of structurally diversified compounds
As 7a–s binds with chain P of 4N5Y for HT29, chain B of 1IGT for MDAMB231 and chain A of 2VWD for HEK293T cancer cell lines. They have selectively bound to glycine (GLY), histidine (HSD), phenyl alanine (PHE), alanine (ALA) of 4N5Y with a binding energy ranging from − 9.0887 to − 7.2184 kcal/mol
An array of novel tetracyclic acridone derivatives (7a–s) have been synthesized in good yields from quinoxaline, where Cs2CO3–Pd(OAc)2–Xantphos used as a potential catalytic system in generating the acridone ring by forming a C–N linkage
Summary
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. Drugs, amongst such compounds acridone derivatives plays a key role as acridine based natural and synthetic compounds are a vital class of nitrogen heterocycles. These compounds are attentive as they exhibit an extensive array of pharmaceutical properties as it is being an integral part of natural products and important heterocycles in medicinal chemistry. On the other hand acrifoline (VII), chlorospermine A (VIII) and chlorospermine B (IX) were reported as potential inhibitor of DYRK1A, a therapeutic cancer target which regulates the cell cycle progression of tumors and o ncogenes[24,25]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
