Discovery of NewS‐Glycosides andN‐Glycosides of Pyridine‐biphenyl System with Antiviral Activity and Induction of Apoptosis inMCF7 Cells

Abstract

Glycosylation of small molecule‐based drugs can dramatically improve the biological activities of the parent scaffold. In the current study, S‐glycosides and N‐glycosides of polyfunctionalized pyridine‐biphenyl system tethered with benzotriazole moiety were designed and synthesized. S‐Glycosides of pyridine‐2‐thione derivatives 5a–h and N‐glycosides of pyridine‐2‐one derivatives 9a,b were synthesized by a facile, convenient, and high‐yielding procedure. The epimers glucose and galactose, acetylated or deacetylated, were used to form the glycone part. The structures of these compounds were confirmed by microanalysis and spectroscopic data (IR, 1H–NMR, and 13C‐NMR). The anticancer activities of the target compounds, in comparison with standard cisplatin, were assessed by MTT assay against MCF7 cell line. Compounds 4f, 4g, 5f, and 5h exhibited the highest cytotoxic effect on MCF7. The anticancer effect of these four compounds induced the apoptosis as evident by the up‐regulated expression of the apoptotic genes Bax and p53 and down‐regulated expression of the anti‐apoptotic gene BCl2. S‐Glycoside derivatives are more active than N‐glycosides. Moreover, the nontoxic doses of the tested compounds were evaluated in MA104, FRHK4, BGM, Hep2, and Vero cells. Compounds 4a–d and 5a–d were also evaluated for their antiviral effect against HSV‐1, HAV, and rotavirus Wa strain. The compounds' results showed less, moderated, and high antiviral activities. The docking study for these compounds with MDM2 revealed that deacetylated galactose is important for binding with the receptor as it facilitates the formation of hydrogen bond in the receptor. Rapid overlay of chemical structures analysis was employed to understand the compounds' similarity on the basis of their shape structure using the Tanimoto scores.

Synthesis and Bioactivities of Novel 1,3,4-Thiadiazole Derivatives of Glucosides

“…Glycosides are secondary metabolites that widely exist in all organs of plants, such as flowers, fruits, leaves, skins, and roots, etc ( Gruner et al, 2002 ), and previous studies found that glycosides had a wide range of pharmacological activities, such as antiviral ( Chen W. et al, 2019 ; Khodair et al, 2019 ), antibacterial ( Mohammed et al, 2019 ), anticancer ( Gurung et al, 2018 ; Rahim et al, 2020 ), antioxidant ( Jiang et al, 2018 ; Hawas et al, 2019 ), and anti-HIV ( He et al, 2019 ) activities. Meanwhile, studies also found that glycoside derivatives showed exceeding inhibitory activities against plant pathogens.…”

Therapeutic effect of Arthrocnemum machrostachyum methanolic extract on Ehrlich solid tumor in mice

“…This is crucial for cancer cells to maintain their uncontrollable proliferation. Therefore, triggering apoptosis is a main mode of action for most of the anti-cancer agents [16,17,19,[42][43][44][45]. In the present study, A. machrostachyum extract reduces EST size through induction of apoptosis as evidenced histologically (presence of apoptotic cells), and molecularly (up-regulation of the apoptotic genes p53, Bax, and caspase 3, and downregulation of the antiapoptotic gene Bcl2 as well as increase DNA damage).…”

New N-ribosides and N-mannosides of Rhodamine Derivatives for Suppressing Leukemia Cell Line Growth

“…Rapid Overlay Chemical Similarity (ROCS) study was operated to explain the similarity of the compounds and to figure out the most important pharmacophoric features. Glycosides of structurally similar heterocyclic systems have been reported before [7][8][9][10][11][12][13][14][15].…”