Synthesis of 3-Trifluoromethyl-5,6-dihydro-[1,2,4]triazolo Pyrazine Derivatives and Their Anti-Cancer Studies

Abstract

The synthesis of a wide variety of 3-trifluoromethyl-5,6-dihydro-[1,2,4]triazolo pyrazine derivatives, by the treatment of 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-α]pyrazine hydrochloride with an array of isocyanates in the presence of triethylamine, is reported. All the target compounds were synthesized in excellent yields under mild reaction conditions. The target molecules were effectively screened for their anti-cancer properties and the results are promising. The resultant compounds were assessed for their antiproliferative action against two human colon cancer cell lines (HCT-116 and HT-29 colon cancer cell lines). The IC50 range was estimated at 6.587 to 11.10 µM showing that compound RB7 had remarkable anticancer movement on HT-29. Additionally, it was discovered that RB7 incited the mitochondrial apoptotic pathway by up-regulating Bax and down-regulating Bcl2, eventually leading to the activation of Caspase 3 in HT-29 cells and initiation of cell death via the mitochondrial apoptotic pathway.

Assessment of the Antimicrobial and Antiproliferative Activities of Chloropyrazine-Tethered Pyrimidine Derivatives: In Vitro, Molecular Docking, and In-Silico Drug-Likeness Studies

“…Examples of drugs with a pyrimidine nucleus are antibacterial and antimalarial agents targeting the folate pathway: trimethoprim, iclaprim, sulfadimethoxine, pyrimethamine, and sulfadoxine; antimetabolite and ergosterol biosynthesis inhibitor antifungal drugs: flucytosine and voriconazole; antimetabolite anti-cancer agents: 5-fluorouracil and capecitabine; tyrosine kinase inhibitors: imatinib, dasatinib, and nilotinib; antivirals: ara-c, idoxuridine, zidovudine, stavudine, lamivudine, and emtricitabine; and the antitubercular drug capreomycin (Figure 1). Many substituted pyrazine derivatives were reported with potential antibacterial [6][7][8][9][10][11], antifungal [12][13][14][15], anticancer [16][17][18][19][20][21], antioxidant [22][23][24][25], and antitubercular [9,[26][27][28] activities. Similarly, pyrimidine-based compounds also showed excellent antimicrobial (antibacterial and antifungal) [29][30][31][32][33], antimycobacterial [34][35][36][37][38], antioxidant [39][40][41][42], cytotoxic and anticancer [42][43][44]…”