Novel Pyrimidinone Derivatives: Synthesis, Antitumor and Antimicrobial Evaluation

Abstract

Starting from 6-aryl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (4a-d), a series of mono-and dialkyl derivatives 5a-j and 6a, b was synthesized. Hydrazinolysis of 4a, b, d and 5d afforded the hydrazino derivatives 7a-c which were cyclised to give the triazolopyrimidinones 8a-c and the pyrimidotriazinones 9a-c through the reaction with formic acid and chloroacetyl chloride, respectively. Most of the newly synthesized compounds were evaluated for their in-vitro antitumor activity. Compounds 6a and b displayed promising anticancer activity against leukaemia, non-small cell lung, melanoma, and renal cancer. On the other hand, all compounds prepared were screened for their in-vitro antibacterial and antifungal activities. Compounds 5h and j showed significant activity against Staphylococcus aureus, while compounds 5e, 7c and 8c displayed moderate inhibitory activity against Candida albicans.Key words pyrimidinone; synthesis; antitumor activity; antimicrobial activity Nowadays, cancer is the highly striking disease worldwide. It represents the second leading cause of human mortality after cardiovascular diseases. During the search for developing more potent anticancer agents, several nitrogen heterocycles were synthesized and evaluated for their anticancer activity.

Synthesis, Antitumor and Antimicrobial Testing of Some New Thiopyrimidine Analogues

“…7,14) 2-Alkylthio-6-aryl-4-chloropyrimidine-5-carbonitrile (3a-d) A suspension of 2a-d (0.0017 mol) and phosphorus oxychloride (6 mL) was heated under reflux for 5 h. Excess phosphorus oxychloride was evaporated under reduced pressure to half its volume. The reaction mixture was poured onto ice cold water (15 mL) with continuous stirring.…”

“…The development of potent and effective novel antineoplastic drugs is one of the most intensely persuaded goals of contemporary medicinal chemistry. In view of the biological significance of thiouracils and in continuation of our previous efforts in the synthesis of new thiouracils and uracil-related heterocycles, 7) we would like to report herein the synthesis of new thioxo-chloro-pyrimidines (3b-d), substituted-aminopyrimidines (4a-g) and thiazolopyrimidines (5a-c, 6a-h) and their antitumor, antimicrobial testing. …”

“…[2][3][4][5] S-Alkylation (B) and N-alkylation (C) products of thiouracil analogues have been recently reported as novel antibacterial, and cytotoxic agents. 6,7) Thiazolopyrimidines (D), the bioisostere analogues of the anticancer purines such as Thioguanine 8,9) (Lanvis ® ) (E), are potentially bioactive molecules reported to display significant anticancer and antimicrobial activities [10][11][12][13] (Fig. 1).…”

Synthesis of Novel Substituted Tetrahydropyrimidine Derivatives and Evaluation of Their Pharmacological and Antimicrobial Activities

“…Recently, it was reported that some series of 5‐cyano‐2‐thiouracil derivatives showed antimicrobial activities against Staphylococcus aureus , Bacillus subtilis , and Escherichia coli besides their remarkable antifungal activity against Candida albicans and Aspergillus niger . Furthermore, thiouracils exhibited potential therapeutics as antiviral, anticancer, and antimicrobial agents . For example, S ‐alkylation and N ‐alkylation products of pyrimidine‐2‐thione have been recently reported as novel antibacterial, cytotoxic agents , and unique HIV reverse transcriptase inhibitors‐.…”

Synthesis and evaluation of cytotoxicity of 6-amino-4-aryl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitriles

“…Thio substituted pyrimidine derivatives occupy a special position among these compounds. They are also identified as potential antimicrobial and antican cer [11][12][13][14][15][16][17][18], as well as anti inflammatory agents [19]. Prompted by these reports and in continuation of our endeavor on potential anticancer agents [20,21], we have now focused our attention on preparing a series of 6 amino 4 phenyl 2 thioxo 1,2,3,4 tetrahydro pyrimidine 5 carbonitriles (I)-(X) and screened them for antiproliferative activity against human breast cancer (MCF 7), human colon carcinoma (HT29), and non malignant mouse fibroblast (L929) cell lines.…”