33301-21-2Relevant academic research and scientific papers
Dengue virus replication inhibition by dibenzothiepin derivatives
Mihai, Dragos P.,Nitulescu, George M.,Smith, Jessica L.,Hirsch, Alec J.,Stecoza, Camelia E.
, p. 320 - 328 (2019)
The presented research uses both a target-based drug design strategy focused on dengue virus (DENV) helicase, and the repurposing of a known scaffold, the dibenzo[b,e]thiepine moiety, extensively used in antidepressants drugs. A series of dihydrodibenzo[b,e]thiepin derivatives were synthesized and tested at 10 μg/mL in HEK293 cells infected with DENV2. The replication inhibitory effect was average and depends on the chemical structure. The best antiviral effect was recorded for compounds, (E)-(2-methyl-6,11-dihydrodibenzo[b,e]thiepin-11-ylidene)amino butanoate (TM3) and (E)-(2-methyl-6,11-dihydrodibenzo[b,e]thiepin-11-ylidene)amino 3-fluorobenzoate (TM24); the concentrations resulting in a 90% (1 log) inhibiton of viral titers (IC90) being calculated at 10 μM for TM3 and 0.25 μM for TM24. A molecular docking study has been conducted in order to predict the binding affinity of the tested compounds to DENV2 NS3 helicase and also on dopamine D4 receptor and to establish an in silico–in vitro correlation. The results obtained indicate that the antiviral mechanisms are complex and differ significantly depending on the structure. The majority of compounds appear to inhibit only the viral helicase, some of them both helicase and D4 receptors, and in the case of one compound the mechanism is elusive. We also observed that a 2-methyl substitution and S-oxidation on the dibenzo[b,e]thiepin scaffold significantly improves the inhibition of the viral replication.
New Triazine Derivatives as Potent Modulators of Multidrug Resistance
Dhainaut, Alain,Regnier, Gilbert,Atassi, Ghanem,Pierre, Alain,Leonce, Stephane,et al.
, p. 2481 - 2496 (2007/10/02)
A series of 70 triazine derivatives have been synthesized and tested for their capacity to modulate multidrug resistance (MDR) in DC-3F/AD and KB-A1 tumor cells in vitro, in comparison with verapamil (VRP), a calcium channel antagonist currently used in therapy as an antihypertensive drug, which also shows MDR modulating activity.Among the 12 selected compounds, 16 (S9788) showed high MDR reversing properties in vitro (300- and 6-fold VRP at 5μM in DC-3F/AD and KB-A1 cells, respectively) and induced a strong accumulation of adriamycin.The relationship between the increase of ADR accumulation and the fold reversal induced by these compounds and their lack of effects on the sensitive DC-3F cells suggest that they act mainly by inhibiting the P-glycoprotein (Pgp) catalyzed efflux of cytotoxic agents, as already described for a majority of MDR modulators.In vivo, in association with the antitumor drug vincristine (0.25 mg/kg), 16 (100 mg/kg) increased the T/C by 39percent in mice bearing the resistant tumor cell line P388/VCR.According to these interesting properties, 16 was selected for a clinical development because it is more bioavailable than 34, even though it was less active.
