Synthesis of 5-haloethynyl- and 5-(1,2-dihalo)vinyluracil nucleosides: Antiviral activity and cellular toxicity

5-Alkynyl Analogs of Arabinouridine and 2‘-Deoxyuridine: Cytostatic Activity against Herpes Simplex Virus and Varicella-Zoster Thymidine Kinase Gene-Transfected Cells

“…The 2‘-deoxyribo compounds were virtually not cytotoxic (as their arabino counterparts) (MCC ≥ 50 μM) but markedly more cytostatic (CC 50 = 0.18 to 2.5 μM range) than the arabino compounds (CC 50 = 20 to >200 μM range). These anti-CMV and cell cytotoxicity (CC 50 ) data are consistent with previous studies showing that (i) EDU is more potent than EAU against CMV, (ii) EDU is more cytostatic than EAU, (iii) IEDU is a more potent anti-CMV agent than ribavirin, and (iv) IEDU is very cytostatic to PBM and CEM cells . The high cytostatic activity of the 5-alkynyl-2‘-deoxyuridines may likely be due to inhibition of TS and subsequent inhibition of cellular DNA synthesis.…”

“…The Sonogashira coupling reaction of 5-iodo-2‘-deoxyuridine ( 5 ) with Me 3 SiC⋮CH in the presence of (PPh 3 ) 2 PdCl 2 and CuI in Et 3 N and MeCN afforded TMSEDU ( 6 , 79%), as illustrated in Scheme . Although we and others have protected the sugar hydroxyl groups as acetates, , p -chlorobenzoates, or p -toluoates 9 when a Sonogashira coupling reaction is employed, the reaction works equally well with the unprotected 5-iodo-2‘-deoxyuridine ( 5 ). The TMS group in TMSEDU was readily removed by treatment with 0.05 N NaOMe to yield the previously reported 9 EDU ( 7 , 87%).…”

“…These anti-CMV and cell cytotoxicity (CC 50 ) data are consistent with previous studies showing that (i) EDU is more potent than EAU against CMV, 9 (ii) EDU is more cytostatic than EAU, 9 (iii) IEDU is a more potent anti-CMV agent than ribavirin, 20 and (iv) IEDU is very cytostatic to PBM and CEM cells. 20 The high cytostatic activity of the 5-alkynyl-2′-deoxyuridines may likely be due to inhibition of TS and subsequent inhibition of cellular DNA synthesis.…”

An easy microwave-assisted synthesis of C8-alkynyl adenine pyranonucleosides as novel cytotoxic antitumor agents

“…Alkynyl-modified nucleosides and especially pyrimidine derivatives substituted at C 5 and purine derivatives substituted at C 8, have been shown to possess interesting biological properties (Lin et al, 1985 ; Meneni et al, 2007 ; Lee et al, 2009 ; Vivet-Boudou et al, 2011 ). Some representative examples include 5-ethynyl-2′-deoxyuridine, which exhibited antiproliferative activity against human breast cancer cells, exceeding that of cisplatin and 5-fluorouracil, while 5-bromoethynyluridine demonstrated significant anti-HCV properties (Escuret et al, 2005 ; Meneni et al, 2007 ). Although, little effort has been made toward the synthesis of C 8-modified purine nucleosides, in some cases, interesting biological properties have been reported, such as some 8-alkynyl adenosines, which proved to be very selective ligands for the A 3 adenosine receptor subtype behaving as adenosine antagonists (Volpini et al, 2001 ) and various C 8-modified 2′-deoxy adenosines, which induced delayed chain termination in vitro and showed moderate anti HIV-1 activity in cell culture (Vivet-Boudou et al, 2011 ).…”

Deoxygenation of 5-O-benzoyl-1,2-isopropylidene-3-O-imidazolylthiocarbonyl-α-d-xylofuranose using dimethyl phosphite: an efficient alternate method towards a 3′-deoxynucleoside glycosyl donor

“…The removal of the 3 0 -hydroxy group in nucleoside analogues, leading to the corresponding 3 0 -deoxy compounds is a well-known chemical modification, explored by several research groups in the aim to improve the antiviral and/or antineoplastic, [1][2][3][4][5] or more recently the anti-SARS-CoV 6,7 activities of modified nucleosides.…”