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  • Rifampicin that is methyl piperazinyl

    2022-05-26

    Rifampicin, that is 3-[[(4-methyl-1-piperazinyl) imino] methyl]-rifamycin (Fig. 1), is a semisynthetic antibiotic drug. It is one of the most potent and broad drug against bacterial pathogens and tuberculosis [9]. In recent years, rifampicin has also been reported to have inhibitory effects on Taq RNA polymerase [10], amyloid β protein aggregation [11], and tyrosinase [12]. Nevertheless, to our knowledge, the inhibitory kinetic and mechanism of rifampicin on α-glucosidase have not been reported up to now.
    Experimental
    Results and discussion
    Conclusions
    Acknowledgements This work was supported financially by the Natural Science Foundation of China (No. 31501414), Jiangxi Province Natural Science Fund (No. 20171BAB214019), Project of Education Department of Jiangxi Province (No. GJJ150302) and Provincial Graduate Innovation Fund Project of Jiangxi Province (No. YC2017-S151).
    Introduction α-Glucosidase is a digestive enzyme, which plays a vital role in the breakdown of disaccharide and polysaccharides in the intestine [1]. α-Glucosidase inhibitors could diminish postprandial plasma dexamethasone acetate australia levels and, as a result, they decreased postprandial hyperglycemia. Therefore, α-glucosidase is an essential target for the treatment of type 2 diabetes [2]. Furthermore, α-glucosidase also has been introduced as an attractive therapeutic target for dexamethasone acetate australia other carbohydrate-mediated diseases including HIV, cancer, and hepatitis [[3], [4], [5]]. Acarbose, miglitol, and voglibose are α-glucosidase inhibitors that have been approved for the clinical use. These drugs have side effects such as flatulence, pain, bloating, diarrhea, and abdominal discomfort [6]. Hence, the search for new agents with high α-glucosidase inhibitory activity and low side effects is still in progress [[7], [8], [9]]. Thiosemicarbazide and thiourea are two sulfur-containing scaffolds, which are found in the many biologically active compounds with antitumor, antibacterial, antifungal, anticonvulsant, and antioxidant activities [[10], [11], [12], [13], [14], [15], [16], [17], [18], [19]]. Furthermore, derivatives of these scaffolds such as thiosemicarbazide derivatives A and thiourea derivatives B have been reported to show high inhibitory activity against α-glucosidase (Fig. 1) [20,21]. On the other hand, recently, several groups of α-glucosidase inhibitors containing Schiff-base such as compounds C have been synthesized (Fig. 1) [22]. 1,2,3-Triazole is a five-membered ring with three nitrogen atoms and applied as an important building block in many biologically active compounds with various pharmacological activities [[23], [24], [25]]. One of the reported pharmacological effects of 1,2,3-triazole derivatives is α-glucosidase inhibition [[26], [27], [28], [29]]. In Rodinia respect, newly, our research group by using molecular hybridization reported a new series of 1,2,3-triazole-quinazolinone hybrids D as potent α-glucosidase inhibitors [30]. Therefore, herein, with focusing on structures A, B, C, and D as potent α-glucosidase inhibitors, a new series of thiosemicarbazide-1,2,3-triazole hybrids 10a-o are designed as the follow up efforts in the development of new α-glucosidase inhibitors by molecular hybridization [[31], [32], [33]]. Designed compounds were synthesized and evaluated against α-glucosidase. Kinetic and docking studies were also performed to assay the interaction of these compounds with α-glucosidase.
    Method and material Melting points of the target compounds 10a-o was measured on a Kofler hot stage apparatus. 1H and 13C NMR spectra of title compounds were determined on a Bruker FT-500 via TMS (internal standard). IR spectra re-coded using KBr disks on a Nicolet Magna FTIR 550 spectrophotometer. Mass spectra for selected compounds 10a, 10d, and 10l were obtained with an Agilent Technology (HP) mass spectrometer operating at an ionization potential of 70 eV. Elemental analysis was performed by an Elementar Analysen system GmbH VarioEL CHN mode.