Amino acid esters substituted phosphorylated emtricitabine and didanosine derivatives as antiviral and anticancer agents.
Owing to the promising antiviral activity of amino acid ester-substituted phosphorylated nucleosides in the present study, a series of phosphorylated derivatives of emtricitabine and didanosine substituted with bioactive amino acid esters at P-atom were synthesized. Initially, molecular docking studies were screened to predict their molecular interactions with hemagglutinin-neuraminidase protein of Newcastle disease virus and E2 protein of human papillomavirus. The title compounds were screened for their antiviral ability against Newcastle disease virus (NDV) by their in ovo study in embryonated chicken eggs. Compounds 5g and 9c exposed well mode of interactions with HN protein and also exhibited potential growth of NDV inhibition. The remaining compounds exhibited better growth of NDV inhibition than their parent molecules, i.e., emtricitabine (FTC) and didanosine (ddI). In addition, the in vitro anticancer activity of all the title compounds were screenedagainst HeLa cell lines at 10 and 100 μg/mL concentrations. The compounds 5g and 9c showed an effective anticancer activity than that of the remaining title compounds with IC50 values of 40 and 60 μg/mL, respectively. The present in silico and in ovo antiviral and in vitro anticancer results of the title compounds are suggesting that the amino acid ester-substituted phosphorylated FTC and ddI derivatives, especially 5g and 9c, can be used as NDV inhibitors and anticancer agents for the control and management of viral diseases with cancerous condition.
Department of Chemistry, Sri Venkateswara University, Tirupati, 517502, India.
Kuruva Chandra
KC
Sekhar
Avilala
A
Janardhan
Yellapu Nanda
YN
Kumar
Golla
G
Narasimha
Chamarthi Naga
CN
Raju
S K
SK
Ghosh
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002642:Chick Embryo; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016049:Didanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D000068679:Emtricitabine; D004951:Esterification; D015707:HN Protein / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D009522:Newcastle disease virus / Q000187:drug effects; D027383:Papillomaviridae / Q000187:drug effects; D010766:Phosphorylation; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000187:drug effects
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D015707:HN Protein; D014764:Viral Proteins; D003841:Deoxycytidine; D000068679:Emtricitabine; D016049:Didanosine