Efficient synthesis and evaluation of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives as antiproliferative agents.

Based on our previous work, a series of novel 6-arylamino-[1,2,4]triazolo[4,3-a]pyridine derivatives were synthesized, and evaluated for antiproliferative activities. SAR studies revealed that inserting an amino linkage between 6­aryl group and [1,2,4]triazolo[4,3-a]pyridine core led to amuch broaderantitumorspectrum, and the most promising compound 8 l exerted potent andbroad-spectrum antiproliferative activity toward HeLa, HCT116, MCF-7, and A549 cell lines, with IC50 values in the micromolar range of 5.98-12.58 µM, which were more active than the positive control 5-FU. The mechanism investigation illustrated that 8 l dose-dependently caused cell cycle arrest at the G2/M phase, and induced cell apoptosis in HeLa cells. Consequently, these findings suggest the 6-arylamino-[1,2,4]triazolo[4,3-a]pyridines afford significant potential for the discovery of a new highly efficient anticancer agents.

The role of nitro group on the excited-state relaxation mechanism of P-Z base pair.

DNAs' photostability is significant to the normal function of organisms. P-Z is a hydrogen bonded artificial DNA base pair, where P and Z represent 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)one and 6-amino-5nitro-2(1H)-pyridone, respectively. The excited-state relaxation mechanism of P-Z pair is investigated using static TDDFT calculations combined with the non-adiabatic dynamic simulations at TDDFT level. The roles of nitro rotation, nitro out-of-plane deformation, and single proton transfer (SPT) along hydrogen bond are revealed. The results of potential energy profile calculations demonstrate that the SPT processes along the hydrogen bonds are unfavorable to occur statically, which is in great contrast to the natural base pair. The non-adiabatic dynamic simulations show that the excited-state nitro rotation and nitro out-of-plane deformation are the two important relaxation channels which lead to the fast internal conversion to S0 state. The SPT from Z to P is also observed, followed by distortion on P, inducing the fast internal conversion to S0 state. However, this channel (decay via SPT process) plays minor roles on the excited-state relaxation mechanism statistically. This work shows the great differences of the excited-state relaxation mechanism between the natural base pairs and artificial base pair, also sheds new light into the role of hydrogen bond and nitro group in P-Z base pair.