17532-19-3Relevant articles and documents
Synthesis and bioactive evaluations of novel benzotriazole compounds as potential antimicrobial agents and the interaction with calf thymus DNA
Ren, Yu,Zhang, Hui Zhen,Zhang, Shao Lin,Luo, Yun Lei,Zhang, Ling,Zhou, Cheng He,Geng, Rong Xia
, p. 2251 - 2260 (2015)
A novel series of benzotriazole derivatives were synthesized and characterized by NMR, IR and MS spectra. The bioactive assay manifested that most of the new compounds exhibited moderate to good antibacterial and antifungal activities against the tested strains in comparison to reference drugs chloromycin, norfloxacin and fluconazole. Especially, 2,4-dichlorophenyl substituted benzotriazole derivative 6f displayed good antibacterial activity against MRSA with MIC value of 4 μg/mL, which was 2-fold more potent than Chloromycin, and it also displayed 3-fold stronger antifungal activity (MIC = 4 μg/mL) than fluconazole (MIC = 16 μg/mL) against Beer yeast. The preliminary interactive investigations of compound 6f with calf thymus DNA revealed that compound 6f could effectively intercalate into DNA to form compound 6f-DNA complex which might block DNA replication to exert antimicrobial activities. Molecular docking experiments suggested that compound 6f projected into base-pairs of DNA hexamer duplex forming two hydrogen bonds with guanine of DNA. The theoretical calculations were in accordance with the experimental results.
Further SAR studies on natural template based neuroprotective molecules for the treatment of Alzheimer's disease
Singh, Yash Pal,Shankar, Gauri,Jahan, Shagufta,Singh, Gourav,Kumar, Navneet,Barik, Atanu,Upadhyay, Prabhat,Singh, Lovejit,Kamble, Kajal,Singh, Gireesh Kumar,Tiwari, Sanjay,Garg, Prabha,Gupta, Sarika,Modi, Gyan
, (2021/09/04)
In our earlier paper, we described ferulic acid (FA) template based novel series of multifunctional cholinesterase (ChE) inhibitors for the management of AD. This report has further extended the structure–activity relationship (SAR) studies of this series of molecules in a calibrated manner to improve upon the ChEs inhibition and antioxidant property to identify the novel potent multifunctional molecules. To investigate the effect of replacement of phenylpiperazine ring with benzylpiperazine, increase in the linker length between FA and substituted phenyl ring, and replacement of indole moiety with tryptamine on this molecular template, three series of novel molecules were developed. All synthesized compounds were tested for their acetyl and butyryl cholinestrases (AChE and BChE) inhibitory properties. Enzyme inhibition and PAS binding studies identified compound 13b as a lead molecule with potent inhibitor property towards AChE/BChE (AChE IC50 = 0.96 ± 0.14 μM, BChE IC50 = 1.23 ± 0.23 μM) compared to earlier identified lead molecule EJMC-G (AChE IC50 = 5.74 ± 0.13 μM, BChE IC50 = 14.05 ± 0.10 μM, respectively). Molecular docking and dynamics studies revealed that 13b fits well into the active sites of AChE and BChE, forming stable and strong interactions with key residues Trp86, Ser125, Glu202, Trp 286, Phe295, Tyr 337 in AChE, and with Trp 82, Gly115, Tyr128, and Ser287 in BChE. The compound, 13b was found to be three times more potent antioxidant in a DPPH assay (IC50 = 20.25 ± 0.26 μM) over the earlier identified EJMC-B (IC50 = 61.98 ± 0.30 μM) and it also was able to chelate iron. Co-treatment of 13b with H2O2, significantly attenuated and reversed H2O2-induced toxicity in the SH-SY5Y cells. The parallel artificial membrane permeability assay-blood brain barrier (PAMPA-BBB) revealed that 13b could cross BBB efficiently. Finally, the in-vivo efficacy of 13b at dose of 10 mg/kg in scopolamine AD model has been demonstrated. The present study strongly suggests that the naturally inspired multifunctional molecule 13b may behave as a potential novel therapeutic agent for AD management.
MULTIVALENT RAS BINDING COMPOUNDS
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Paragraph 00807, (2017/07/23)
Described herein are compounds that modulate Ras signaling, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds, and methods of using such compounds in the treatment of conditions, diseases, or disorders associated with altered Ras signaling. Further described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments comprising such compounds and methods of using such compounds in the treatment of cell proliferative disorders, including cancer.
