17532-19-3Relevant academic research and scientific papers
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.
Synthesis and evaluation of aryl substituted propyl piperazines for potential atypical antipsychotic activity
Singh, Shalu,Bali, Alka,Peshin, Tania
, p. 429 - 441 (2021/03/26)
Background: Schizophrenia is a disorder with complex etiology with hyperdopaminer-gia as the leading underlying cause. Atypical antipsychotics are the agents which do not give rise to significant extrapyramidal side effects and are more effective against negative symptoms of schizophrenia. Introduction: A new series of chloro-substituted substituted aryloxypiperazine derivatives and their indole based derivatives was designed and evaluated for atypical antipsychotic activity based on established models for combined dopaminergic and serotonergic antagonism. Method: The present series of compounds were designed based on 3D similarity studies, synthesized and evaluated for atypical antipsychotic activity in animal models for combined dopaminer-gic and serotonergic antagonism. The blood-brain barrier penetration potential was assessed from theoretical log BB values computed through an online software program. Results: Theoretical ADME profiling of the designed compounds based on selected physicochem-ical parameters suggested excellent compliance with Lipinski’s rules. The log BB values obtained for the compounds suggested a good potential for brain permeation. Indole substitution contributed towards an improved efficacy over aryloxy analogs. Lead compounds showed a potential for combined dopaminergic and serotonergic antagonism. Conclusion: The 5-methoxy indole based compounds 16 and 17 were identified as the lead compounds displaying a potential atypical antipsychotic profile.
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.
Piperazine-containing myricetin derivative and preparation method thereof (by machine translation)
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Paragraph 0040; 0042; 0043, (2019/08/07)
The invention discloses a piperazine-amide-containing myricetin derivative, and is characterized in that the general formula is as shown in the specification: Wherein, R1 More than one hydrogen atom, methoxy, nitro, methyl, trifluoromethyl or halogen atom is contained in the ortho, meta or para position on the phenyl ring. The compound has certain inhibitory activity on hepGG2 cells and SGCCCC7901 cells, is small in toxicity to normal cells, and can be used for preparing anti-tumor drugs. (by machine translation)
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.
Synthesis and evaluation of meta substituted 1-(aryloxypropyl)-4- (chloroaryl) piperazines as potential atypical antipsychotics
Bali, Alka,Reddy, A. C. Dinesh Kumar
, p. 382 - 391 (2013/03/13)
A series of 1-(aryloxypropyl)-4-(chloroaryl) piperazines have been synthesized based upon their physicochemical similarity with respect to standard atypical antipsychotic drugs and their potential to cross the blood-brain barrier (log BB) as calculated by
Synthesis and computational studies on aryloxypropyl piperazine derivatives as potential atypical antipsychotic agents
Bali, Alka,Bhalla, Abhishek,Bala, Suman,Kumar, Rajesh
scheme or table, p. 218 - 224 (2012/07/17)
A series of aryloxypropyl derivatives have been synthesized and evaluated for atypical antipsychotic activity in apomorphine induced mesh climbing and stereotypy assays in mice and the compounds displayed good efficacy coupled with an atypical profile. In
Gas-phase nucleophilic aromatic substitution between piperazine and halobenzyl cations: Reactivity of the methylene arenium form of benzyl cations
Chai, Yunfeng,Jiang, Kezhi,Sun, Cuirong,Pan, Yuanjiang
body text, p. 10820 - 10824 (2011/11/07)
Methylene arenium involved in SNAr: The gas-phase nucleophilic aromatic substitution reactions of halobenzyl cations with piperazine through a cationic σ complex were studied using ESI mass spectrometry. This study demonstrates that the methylene arenium form of halobenzyl cations exhibits nucleophilic substitution reactivity at the phenyl ring (see scheme). Copyright
Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors
Zhang, Cunlong,Tan, Chunyan,Zu, Xuyu,Zhai, Xin,Liu, Feng,Chu, Bizhu,Ma, Xiaohua,Chen, Yuzong,Gong, Ping,Jiang, Yuyang
experimental part, p. 1404 - 1414 (2011/04/22)
Based on the literature-reported compensatory effect of PI3K on Abl inhibition and the improved preclinical effect of drug combination of Abl and PI3K inhibitors, a series of compounds bearing novel scaffold of (S)-3-aminopyrrolidine was identified as Abl and PI3K dual inhibitors through support vector machine screening tool, which were subsequently synthesized and tested. Most compounds demonstrated promising cytoxicity against a CML leukemia cell-line K562 and moderate inhibition against Abl and PI3K kinases. These compounds induced no apoptosis in K562 cell-line, suggesting that their cytotoxic activities are unlikely duo to other known anti-CML mechanisms. Molecular docking study further showed that the compound 5k could bind with both Abl and PI3K, but the weaker binding with Abl compared to Imatinib is consistent with its low kinase inhibitory rates. These plus literature-reported evidences suggest that the promising cytotoxic effect of our novel compounds might be due to the collective effect of Abl and PI3K inhibition.
Synthesis, evaluation and computational studies on a series of acetophenone based 1-(aryloxypropyl)-4-(chloroaryl) piperazines as potential atypical antipsychotics
Bali, Alka,Sharma, Komal,Bhalla, Abhishek,Bala, Suman,Reddy, Dinesh,Singh, Anant,Kumar, Anil
experimental part, p. 2656 - 2662 (2010/07/09)
A series of 1-(aryloxypropyl)-4-(chloroaryl) piperazines have been synthesized and the target compounds evaluated for atypical antipsychotic activity in apomorphine induced mesh climbing and stereotypy assays in mice. The compounds 11 and 12 have emerged
