Design, Synthesis of New Pyridine and Pyrimidine Sugar Compounds as Antagonists Targeting the ERα via Structure-Based Virtual Screening

Abstract

New aryl substituted cyclohepta[b]pyridine and cyclohepta[d]pyrimidine derivatives were synthesized. The sugar hydrazones of the synthesized pyridine and pyrimidine compounds were also prepared. In addition, the 1,3,4-oxadiazolyl acyclic C-nucleoside analogues of the pyridine system were prepared. The haemolytic, Prebiotic, anticancer and antimicrobial activities of some of the synthesized compounds were also studied. Compounds 10 and 12 showed high activity against MCF-7, HEPG-2 and HCT-116 cell lines with IC50 ranged from 3.56-8.55 µg/mL. In addition, the synthesized condensed thiopyrimidine derivative 10 exhibited more potent bactericidal activity while compound 7 demonstrated potent antifungal activity against Aspergillus niger. Furthermore, the synthetic compounds of the pyrimidine base promoted growth of lactic acid bacteria. The predicted binding patterns of three of the prepared derivatives as possible antagonists against ERα were investigated which showed good binding patterns.

Design, Synthesis and Biological Evaluation of Novel Pyrano[2,3-c]pyrazoles And Their Sugar Derivatives as Antimicrobial, Antioxidant and Anticancer Agents

“…Different methods have been reported [11][12][13][14][15][16][17][18] for the synthesis of these derivatives. From the above facts and in continuation of our previous studies for synthesizing and design of novel heterocyclic and their sugar containing derivatives used as potent, selective and anticancer candidates [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] of low toxicity. In the regard to the broad spectrum of biological activities associated with pyrazoles we herein report the synthesis of new pyrano [2,3-c]pyrazole derivatives and their sugar derivatives and screen them in vitro for their antimicrobial, antioxidant, and anticancer activities.…”

Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

“…On the other hand, glycoside and their analogs have been revealed as an important bioactive group of compounds with anticancer, antiviral, and antimicrobial activity. The therapeutic importance of this scaffold motivated us to develop selective procedures for the synthesis of new derivatives of pyridine incorporating pyrazolyl, imidazolyl, thienyl, and glycosyl moieties in which substituents could be arranged in a pharmacophoric pattern to display high order of anticancer activity [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ].…”

Synthesis and Cytotoxic Activity of New Thiazolopyrimidine Sugar Hydrazones and Their Derived Acyclic Nucleoside Analogues

“…Recent strategies of combining various pharmacophoric scaffolds in a new hybrid structure (molecular hybridization) for constructing potent drugs have been reported to result in the formation of more potent bioactive candidates. These significances and our ongoing interest in synthesizing new active carbohydrate based heterocycles [38,[43][44][45][46] prompted us to synthesize new hybrid compounds comprising thiazolopyrimidine system, aryl or thienyl moiety, and acyclic sugar or oxadiazolyl linked to sugar moiety as modified acyclic C-nucleoside analogs and studying their anticancer activity against a number of cancer cell lines. Thiazolopyrimidine is one of the most interesting heterocyclic scaffolds possessing structural similarity to 5-fluorouracil (5-FU)-the well-known cancer metabolite.…”