Synthesis and antiviral properties of arabino and ribonucleosides of 1,3-dideazaadenine, 4-nitro-1,3-dideazapurine and diketopiperazine.
Different arabinosides and ribosides, viz. Ara-DDA or 9(1-beta-D-arabinofuranosyl) 1,3-dideazaadenine (6), Ara-NDDP or 9(1-beta-D-arabinofuranosyl) 4-nitro-1,3-dideazapurine (7), Ara-DKP or 1(1-beta-D-arabinofuranosyl) diketopiperazine (8), Ribo-DDA or 9(1-beta-D-ribofuranosyl) 1,3-dideazaadenine (9) and Ribo-NDDP or 9(1-beta-D-ribofuranosyl) 4-nitro-1,3-dideazapurine (10) have been synthesized as probable antiviral agents. The arabinosides have been synthesized using the catalyst TDA-1 that causes stereospecific formation of beta-nucleosides while a one-pot synthesis procedure was adopted for the synthesis of the ribonucleosides where beta-anomers were obtained in higher yields. All the five nucleoside analogs have been screened for antiviral property against HIV-1 (IIIB), HSV-1 and 2, parainfluenza-3, reovirus-1 and many others. It was observed that arabinosides had greater inhibitory action than ribosides. The compound 7 or Ara-NDDP has shown maximum inhibition of HIV-1 replication than the rest of the molecules with an IC50 of 79.4 microg/mL.
Sinha
Sarika
S
Nucleic Acids Research Laboratory, Department of Chemistry, University of Allahabad, Allahabad, India.
Srivastava
Richa
R
De Clercq
Erik
E
Singh
Ramendra K
RK
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001087:Arabinonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D054659:Diketopiperazines; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects / Q000821:virology; D006801:Humans; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D009690:Nucleic Acid Conformation; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014709:Vero Cells / Q000166:cytology / Q000187:drug effects / Q000821:virology; D014780:Viruses / Q000187:drug effects
C500095:1,3-dideazaadenine; C500096:4-nitro-1,3-dideazapurine; D000998:Antiviral Agents; D001087:Arabinonucleosides; D054659:Diketopiperazines; D009574:Nitro Compounds; D010879:Piperazines; D011687:Purines; D012263:Ribonucleosides; D000225:Adenine