6381-55-1Relevant articles and documents
Novel potent and selective DPP-4 inhibitors: Design, synthesis and molecular docking study of dihydropyrimidine phthalimide hybrids
Mourad, Ahmed A. E.,Khodir, Ahmed E.,Saber, Sameh,Mourad, Mai A. E.
, p. 1 - 24 (2021/02/26)
Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as antihyperglycemic agents that improve glycemic control in type 2 diabetic patients, either as monotherapy or in combination with other antidiabetic drugs. Methods: A novel series of dihydropyrimidine phthalimide hybrids was synthesized and evaluated for their in vitro and in vivo DPP-4 inhibition activity and selectivity using alogliptin as reference. Oral glucose tolerance test was assessed in type 2 diabetic rats after chronic treatment with the synthesized hybrids ± metformin. Cytotoxicity and antioxidant assays were performed. Additionally, molecular docking study with DPP-4 and structure activity relationship of the novel hybrids were also studied. Results: Among the synthesized hybrids, 10g, 10i, 10e, 10d and 10b had stronger in vitro DPP-4 inhibitory activity than alogliptin. Moreover, an in vivo DPP-4 inhibition assay revealed that 10g and 10i have the strongest and the most extended blood DPP-4 inhibitory activity compared to alogliptin. In type 2 diabetic rats, hybrids 10g, 10i and 10e exhibited better glycemic control than alogliptin, an effect that further supported by metformin combination. Finally, 10j, 10e, 10h and 10d had the highest radical scavenging activity in DPPH assay. Conclusions: Hybrids 10g, 10i and 10e are potent DPP-4 inhibitors which may be beneficial for T2DM treatment.
Facile one-pot three-component synthesis of 4,6-diaryl-3,4-dihydropyrimidine-2(1H)-thiones under ultrasonic irradiation
Abbass, Shymaa A.,Moustafa, Gamal A. I.,Hassan, Heba A.,Abuo-Rahma, Gamal El-Din A.
supporting information, p. 2995 - 3000 (2019/08/22)
We developed a facile one-pot procedure for the synthesis of 4,6-diaryl-3,4-dihydropyrimidine-2(1H)-thione under ultrasonic irradiation. The method is based on a three components reaction of aldehydes, ketones, and thiourea under basic conditions affordin
Synergistic antifungal effect of cyclized chalcone derivatives and fluconazole against Candida albicans
Ahmad, Aijaz,Wani, Mohmmad Younus,Patel, Mrudula,Sobral, Abilio J.F.N.,Duse, Adriano G.,Aqlan, Faisal Mohammed,Al-Bogami, Abdullah Saad
, p. 2195 - 2207 (2017/12/26)
The occurrence of invasive fungal diseases, particularly in immunocompromised patients, is life-threatening and increases the economic burden. The rising problem of multi-drug resistance is becoming a major concern for clinicians. In addition, a repertoire of antifungal agents is far less in number than antibacterial drugs. To combat these problems, combination therapy has gained a lot of interest. We previously reported the synergistic interaction of some mono- and bis-dihydropyrimidinone and thione derivatives with fluconazole and amphotericin B for combination antifungal therapy. In this study we used the same approach and synthesized different azole and non-azole derivatives of mono-(M) and bis-(B) chalcones and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drug-fluconazole (FLC)-against seven FLC susceptible and three FLC resistant clinically isolated Candida albicans strains. Based on the minimum inhibitory concentration results, the bis-derivatives showed lower MIC values compared to their mono-analogues. Both fractional inhibitory concentration index and isobologram results revealed mostly synergistic, additive or indifferent interactions between the tested compounds and FLC against different Candida isolates. None of the tested compounds showed any effect on energy dependent R6G efflux, revealing that they do not reverse the mechanism of drug efflux. However, surprisingly, these compounds profoundly decreased ergosterol biosynthesis and showed down regulation of ERG11 gene expression, which is the possible mechanism of reversal of azole drug resistance by these compounds. These results provide a platform for further research to develop pyrimidinone/thione ring containing compounds as promising new antifungal agents, which could be used in antifungal combination therapy.
