- Dammarane sapogenin derivative and preparation method and application thereof
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The invention belongs to the technical field of medicines, and relates to a dammarane sapogenin derivative and a preparation method and application thereof. A series of dammarane sapogenin derivativesare obtained by combining dammarane sapogenins from plants with different groups. Anticancer activity evaluation and anticancer activity mechanism research are carried out on the derivative, and results show that the prepared dammarane sapogenin derivative has a remarkable anticancer effect, has no toxic effect on normal cells and can be used for preparing drugs for treating cancers.
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- Novel panaxadiol triazole derivatives induce apoptosis in HepG-2 cells through the mitochondrial pathway
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In this study, we introduced 1, 2, 4-triazole groups into panaxadiol (PD) to obtain 18 panaxadiol triazole derivatives. Five cancer cells and one normal cell were evaluated for cytotoxicity by MTT assay. The results showed that most of the derivatives could inhibit cancer cell proliferation, and the anti-proliferative activity of compound A1 was the most significant. For HepG-2 cells, the IC50 value was 4.21 ± 0.54 μM, which was nearly 15 times higher than the activity of PD. Further studies showed that compound A1 could induce apoptosis in HepG-2 cells, and could enhance the expression of Cl-caspase-3, Cl-caspase-9 and Cl-PARP. Moreover, Western blot analysis showed that after treating HepG-2 cells with compound A1, the expression of p53 protein was increased and the ratio of Bax/Bcl-2 was gradually increased. The cytoplasmic Bax is then translocated to the mitochondria, causing the release of Cyt c protein. Therefore, the results indicate that compound A1 induces apoptosis through the mitochondrial pathway and can be used the potential to develop new anti-proliferative agents.
- Xiao, Shengnan,Wang, Xude,Xu, Lei,Li, Tao,Cao, Jiaqing,Zhao, Yuqing
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- Synthesis of N′-arylidene-2-(5-aryl-1H-1, 2, 4-triazol-3-ylthio) acetohydrazides as antidepressants
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Abstract: A series of N′-arylidene-2-(5-aryl-1H-1, 2, 4-triazol-3-ylthio) acetohydrazide were synthesized. Condensation of aromatic aldehydes with 2-(5-aryl-1H-1, 2, 4-triazol-3-ylthio) acetohydrazide gave corresponding N′ -arylidene-2-(5-aryl-1H-1, 2, 4-triazol-3-ylthio) acetohydrazide. Spectral and elemental analysis was used for structural elucidation of novel 1, 2, 4-triazole schiff bases. The newly synthesized compounds were screened for their antidepressant activity by using tail suspension test in mice. Compound 4l showed significant activity among the series. Graphical Abstract: A series of new N′-arylidene-2-(5-aryl-1H-1, 2, 4-triazol-3-ylthio)acetohydrazide have been synthesized and characterized. The results revealed that compound 4l with bromo substitution exhibited promising antidepressant activity among the series. [InlineMediaObject not available: see fulltext.].
- Chelamalla, Radhika,Akena, Venkatesham,Manda, Sarangapani
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p. 1359 - 1366
(2017/06/05)
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- Design, synthesis and in silico studies of new 5-substituted-2-(2-(5-aryl-1H-1, 2, 4-triazole-3-ylthio) acetyl) hydrazine carbothioamide/ carbox-amides for anticonvulsant activity
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Background: Research on the synthesis of anticonvulsants is still in progress as they produce adverse effects with lesser activity as well as the patients become resistant to drug therapy. 1,2,4-triazole scaffold is a resource for the synthesis of anticonvulsant agents having better pharmacological action. Virtual Screening plays an important role to achieve binding affinity, receptor and library pre-processing, docking, scoring and top scoring hits. Optimization of drug ADME parameters continues to play an important role to achieve proof of concept, and ultimately efficacy, safely in clinical trials to address unmet medical need. Objective: The aim was to design, synthesise and evaluate anticonvulsant activity of a series of 5-substituted-2-(2-(5-aryl-1H-1,2,4-triazole-3-ylthio)acetyl) hydrazine carbothioamide/ carboxamides along with their in silico properties. Methods: Derivatives of 5-substituted-2-(2-(5-phenyl-1H-1,2,4-triazol-3-ylthio)acetyl)hydrazine carboxamides/ carbothioamides were obtained by condensation of Ethyl-2-(5-aryl-1H-1,2,4-triazol-3-ylthio)acetates with thiosemicarbazide or semicarbazide. The synthesized compounds were characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (1H NMR) and mass spectrometry (MS) while their anticonvulsant activity was screened against pentylenetetrazole-induced seizure (PTZ) against diazepam as reference standard. Molecular docking (in silico) studies were performed using 4-aminobutyrateaminotransferase in order to predict possible protein-ligand interactions. Results: Among the target compounds, 3f exhibited lower activity with 50% protection. The compounds 3e and 3h showed good to moderate levels of anticonvulsant activity with 83.3% protection at 100 mg/kg. The compounds 3g and 3i showed most significant anticonvulsant activity with 100% protection at a dose of 30 mg/kg. In silico results also revealed that 3g and 3i have shown maximum binding affinity to GABA AT protein among the tested compounds. Conclusion: The synthesized compounds showed potent anticonvulsant activity. Molecular docking results should give an insight into how further modification of lead compound can be carried out for higher inhibitory activity.
- Chelamalla, Radhika,Makula, Ajitha,Manda, Sarangapani
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p. 1155 - 1163
(2017/11/14)
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- Synthesis and antidepressant activity of di substituted-5-Aryl-1,2,4- triazoles
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A series of 5-Aryl-1H-1,2,4-triazole-3-thiol (3) were synthesized. Alkylation of thiol group with N,Ndimethyl/ diethyl/dicyclo hexyl-(2-chloro ethyl) amine gave compounds N,N-disubstituted-2-(5-Aryl-1H-1,2,4-triazol-3- ylthio)ethanamine (4). These compounds were characterized on the basis of IR, 1H NMR, Mass spectral data, and elemental analysis. The newly synthesized compounds were screened for their antidepressant activity by using tail suspension test in mice. Springer Science+Business Media, LLC 2011.
- Radhika,Venkatesham,Sarangapani, Manda
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p. 3509 - 3513
(2013/02/25)
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