Synthesis of new 3-acetyl-1,3,4-oxadiazolines combined with pyrimidines as antileishmanial and antiviral agents

Abstract

A new series of 3-acetyl-1,3,4-oxadiazoline hybrid molecules was designed and synthesized using a condensation between acyclonucleosides and substituted phenylhydrazone. All intermediates and final products were screened against Leishmania donovani , a Protozoan parasite and against three viruses SARS-CoV-2, HCMV and VZV. While no significant activity was observed against the viruses, the intermediate with 6-azatymine as thymine and 5-azathymine-3-acetyl-1,3,4-oxadiazoline hybrid exhibited a significant antileishmanial activity. The later compound was the most promising, exhibiting an IC 50 value at 8.98 µM on L. donovani intramacrophage amastigotes and a moderate selectivity index value at 2.4. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11030-022-10548-9.

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

“…A new series of 3-acetyl-1,3,4-oxadiazoline compounds condensed with acyclonucleosides and substituted phenylhydrazone was synthesized and showed moderate activity against herpesviruses. [60] Three compounds, 81, 82 and 83 (Figure 34), showed EC 50 = 46.95 μM, 43.02 μM and 34.38 μM, respectively, against human herpesvirus type 3 (Varicella-Zoster virus -VZV). Compound 81 showed EC 50 = 63.14 μM (strain AD-169) and 44.72 μM (strain Davis) against HMCV.…”

“…A new series of 3-acetyl-1,3,4-oxadiazoline compounds condensed with acyclonucleosides and substituted phenylhydrazone was synthesized and showed moderate activity against herpesviruses. [60] Three compounds, 81, 82 and 83 (Figure 34 The SAR studies showed the important influence of the stereoisomer center on the C-2 carbon of the oxadiazole ring for the antiviral activity, which increased about 4.8 times with the presence of oxadiazole. It was also observed that metachlorine replacement favored the increase in activity.…”

Synthesis and Antioxidant Activities of Novel Pyrimidine Acrylamides as Inhibitors of Lipoxygenase: Molecular Modeling and In Silico Physicochemical Studies

“…A considerable number of clinically used drugs such as minoxidil, phenobarbital, primidone, zidovudine, stavudine, 5-flurouracil, methotrexate, imatinib, dasatinib, pazopanib, nilotinib, cytarabine, uramustine, tegafur, risperidone, sulfamethazine and trimethoprim contain the pyrimidine heterocyclic scaffold [ 14 , 15 ]. In recent years, diverse biological activities of pyrimidine derivatives, including anticancer [ 16 , 17 ], antibacterial [ 18 , 19 , 20 ], antifungal [ 21 ], antitubercular [ 21 , 22 ], antimalarial [ 23 ], antiviral [ 24 , 25 , 26 ], analgesic [ 27 ], antioxidant [ 28 , 29 ], anti-lipoxygenase [ 30 , 31 ] and anti-inflammatory activities have been reported [ 32 , 33 ]. Thus, the pyrimidine ring can be considered as a promising pharmacophoric scaffold for the synthesis of novel bioactive molecules for the treatment of various diseases.…”

Novel 2-Thiouracil-5-Sulfonamide Derivatives: Design, Synthesis, Molecular Docking, and Biological Evaluation as Antioxidants with 15-LOX Inhibition

“…Numerous pyrimidine medicines have a range of therapeutic properties like anticancer such as 5-fluorouracil (5-FU), antiviral such as Idoxuridine and Trifluridine, anti-HIV such as Zidovudine and Stavudine, antibacterial such as Trimethoprim, Sulphamethiazine, and Sulphadiazine, antihypertensive such as Minoxidil and Prazosin, antithyroid such as Propylthiouracil, and antibiotic such as Bacimethrine [ 20 ]. Pyrimidine is a crucial component of nucleic acids, and it is used in pharmaceutics as a building block for the synthesis of anti-inflammatory, anti-hypertensive, antioxidant, anti-SARS [ 21 , 22 , 23 ], antiviral [ 24 ], anticancer [ 25 ], and antibacterial agents [ 26 ].…”