Design, Synthesis, and Biological Evaluation of Novel C5-Modified Pyrimidine Ribofuranonucleosides as Potential Antitumor or/and Antiviral Agents

Abstract

Background: Nucleoside analogues are well-known antitumor, antiviral, and chemotherapeutic agents. Alterations on both their sugar and the heterocyclic parts may lead to significant changes in the spectrum of their biological activity and the degree of selective toxicity, as well as in their physicochemical properties. Methods: C5-arylalkynyl-β-D-ribofuranonucleosides 3-6, 3΄-deoxy 12-15, 3΄-deoxy-3΄-C-methyl- β-D-ribofurananucleosides 18-21 and 2΄-deoxy-β-D-ribofuranonucleosides 23-26 of uracil, were synthesized using a one-step Sonogashira reaction under microwave irradiation and subsequent deprotection. Results: All newly synthesized nucleosides were tested for their antitumor or antiviral activity. Moderate cytostatic activity against cervix carcinoma (HeLa), murine leukemia (L1210) and human lymphocyte (CEM) tumor cell lines was displayed by the protected 3΄-deoxy derivatives 12b,12c,12d, and the 3΄-deoxy-3΄-methyl 18a,18b,18c. The antiviral evaluation revealed appreciable activity against Coxsackie virus B4, Respiratory syncytial virus, Yellow Fever Virus and Human Coronavirus (229E) for the 3΄-deoxy compounds 12b,14, and the 3΄-deoxy-3΄-methyl 18a,18c,18d, accompanied by low cytotoxicity. Conclusion: This report describes the total and facile synthesis of modified furanononucleosides of uracil, with alterations on both the sugar and the heterocyclic portions. Compounds 12b,14 and 18a,c,d showed noticeable antiviral activity against a series of RNA viruses and merit further biological and structural optimization investigations.

Pharmacological Potential of Pyrmidine Derivatives: A Review With Emphasis on Antiviral Effects and Virtual Screening Against Sars‐Cov‐2 Molecular Targets

“…The synthesis of new pyrimidine ribofuranonucleosides with moderate activity against yellow fever virus (YFV) was reported by Kollatos et al. [52] Compounds 63, 64 and 65 showed the best activities with the respective EC 50 of 10.5 � 2.2, 10.5 � 2.2 and 11 � 1.4 μM (Figure 28).…”

Synthesis and Antiviral Efficacy of Pyrimidine Analogs Targeting Viral Pathways

“…Compounds 13 a , 13 b , 13 c , 13 d , 13 e , 13 f have shown moderate activity against cervix carcinoma (HeLa), murine leukemia (L1210) and human lymphocyte (CEM) tumor cell lines. Also, compounds 13 b , 14 and 13 d , 13 e , 13 f displayed noticeable antiviral activity against activity against Coxsackie virus B4, Respiratory syncytial virus, Yellow Fever Virus with low cytotoxicity [119] . 5‐Iodo and phenyl selenenyl substituted pyrimidines have been reported for their potent biological activity, more specifically, antiviral.…”

“…Also, compounds 13b,14 and 13d, 13e, 13f displayed noticeable antiviral activity against activity against Coxsackie virus B4, Respiratory syncytial virus, Yellow Fever Virus with low cytotoxicity. [119] 5-Iodo and phenyl selenenyl substituted pyrimidines have been reported for their…”

Synthesis and Biological Evaluation of Dithiobisacetamides as Novel Urease Inhibitors

“…HepG2, SGC-7901, and K562 cells were grown in RPMI-1640 medium containing 10 % fetal bovine serum and 1 % penicillin/streptomycin at 37 °C in a humidified atmosphere containing 5 % CO 2 , respectively, and cell proliferation was determined as previously described. [31][32] All experiments were performed in triplicate.…”