Novel hit of DPP-4Is as promising antihyperglycemic agents with dual antioxidant/anti-inflammatory effects for type 2 diabetes with/without COVID-19.

DPP-4Is are well recognized therapy for type 2 diabetes. In spite of sharing a common mode of action, the chemical diversity among members of DPP-4Is raised the question whether structural differences may result in distinguished activities. DPP-4Is were recently explored as drug repurposing means for treatment of SARS-CoV-2 due to the urgent need for small molecule drugs for controlling infections. The use of DPP-4Is was not correlated with adverse COVID-19-related consequences among patients with type 2 diabetes. Inspired by these reasons and the importance of pyrimidinone ring as DPP-4I with both antioxidant and anti-inflammatory activities, we succeeded to prepare some novel pyrimidinone and thio-pyrimidinone derivatives, which were then screened for their antidiabetic activity and DPP-4 inhibition. In addition, their anti-inflammatory effect on LPS-stimulated RAW 264.7 cells were evaluated. Furthermore, their antioxidant activities were also tested.

Synthesis and Evaluation of Cytotoxic Activity of Certain Benzo[h]chromene Derivatives.

BACKGROUND: Benzo[h]chromenes attracted great attention because of their widespread biological activities, including anti-proliferate activity, and the discovery of novel effective anti-cancer agents is imperative. OBJECTIVE: The main objective was to synthesize new benzo[h]chromene derivatives and some reported derivatives, and then test all of them for their anti-cancer activities. METHODS: The structures of the newly synthesized derivatives were confirmed by elemental and spectral analysis (IR, Mass, 1H-NMR and 13C-NMR). 35 compounds were selected by the National Cancer Institute (NCI) for single-dose testing against 60 cell lines and 3 active compounds were selected for 5-doses testing. Also, these 3 compounds were tested as EGFR-inhibitors; using sorafenib as standard, and as Tubulin polymerization inhibitors using colchicines as a standard drug. Moreover, molecular docking study for the most active derivative on these 2 enzymes was also carried out. RESULTS: Compounds 1a, 1c and 2b have the highest activities among all 35 tested compounds especially compound 1c. CONCLUSION: compound 1c has promising anti-cancer activities compared to the used standards and may need further modification and investigations.