New structures, chemotaxonomic significance and COX-2 inhibitory activities of cassane-type diterpenoids from the seeds of Caesalpinia minax

RSC Advances ◽  
2015 ◽  
Vol 5 (93) ◽  
pp. 76567-76574 ◽  
Author(s):  
Jian-Long Zhang ◽  
Zhi-Hua Chen ◽  
Jun Xu ◽  
Juan Li ◽  
Ya-Fang Tan ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Inhibitory Activity ◽  
Π Interactions ◽  
Inhibitory Activities ◽  
Cox 2 ◽  
Potent Inhibitory Activity

Eleven new cassane-type diterpenoids, and twelve known compounds were isolated from the seeds of Caesalpinia minax Hance. Some of them displayed potent inhibitory activity against COX-2 through hydrogen bonding and π–π interactions.

GC-MS Investigation and Acetylcholinesterase Inhibitory Activity of Galanthus rizehensis

2013 ◽  
Vol 68 (3-4) ◽  
pp. 118-124 ◽  
Author(s):  
Buket Bozkurt Sarikaya ◽  
Nehir Unver Somer ◽  
Gulen Irem Kaya ◽  
Mustafa Ali Onur ◽  
Jaume Bastida ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Inhibitory Activity ◽  
Gas Chromatography Mass Spectrometry ◽  
Acetylcholinesterase Inhibitory Activity ◽  
Aerial Parts ◽  
Chromatography Mass Spectrometry ◽  
Inhibitory Activities ◽  
Alkaloid Extracts ◽  
Potent Inhibitory Activity

GC-MS (gas chromatography-mass spectrometry) analyses of alkaloids in the aerial parts and bulbs of Galanthus rizehensis Stern (Amaryllidaceae), collected during two different vegetation periods, was performed. Twenty three alkaloids were identified in four different alkaloid extracts. Acetylcholinesterase (AChE) inhibitory activities of the alkaloid extracts were tested. Both the highest alkaloid diversity and the most potent inhibitory activity (IC50 12.94 μg/ml) were obtained in extracts from the bulbs of G. rizehensis collected during the fruiting period.

scholarly journals Development of a Bestatin-SAHA Hybrid with Dual Inhibitory Activity against APN and HDAC

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 4991
Author(s):  
Jiangying Cao ◽  
Wei Zhao ◽  
Chunlong Zhao ◽  
Qian Liu ◽  
Shunda Li ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Inhibitory Activity ◽  
Hdac Inhibitor ◽  
Hdac Inhibitors ◽  
E3 Ubiquitin Ligase ◽  
Hydroxamic Acids ◽  
Dual Inhibitor ◽  
Apoptosis Protein ◽  
Inhibitory Activities ◽  
Potent Inhibitory Activity

With five histone deacetylase (HDAC) inhibitors approved for cancer treatment, proteolysis-targeting chimeras (PROTACs) for degradation of HDAC are emerging as an alternative strategy for HDAC-targeted therapeutic intervention. Herein, three bestatin-based hydroxamic acids (P1, P2 and P3) were designed, synthesized and biologically evaluated to see if they could work as HDAC degrader by recruiting cellular inhibitor of apoptosis protein 1 (cIAP1) E3 ubiquitin ligase. Among the three compounds, the bestatin-SAHA hybrid P1 exhibited comparable even more potent inhibitory activity against HDAC1, HDAC6 and HDAC8 relative to the approved HDAC inhibitor SAHA. It is worth noting that although P1 could not lead to intracellular HDAC degradation after 6 h of treatment, it could dramatically decrease the intracellular levels of HDAC1, HDAC6 and HDAC8 after 24 h of treatment. Intriguingly, the similar phenomenon was also observed in the HDAC inhibitor SAHA. Cotreatment with proteasome inhibitor bortezomib could not reverse the HDAC decreasing effects of P1 and SAHA, confirming that their HDAC decreasing effects were not due to protein degradation. Moreover, all three bestatin-based hydroxamic acids P1, P2 and P3 exhibited more potent aminopeptidase N (APN, CD13) inhibitory activities than the approved APN inhibitor bestatin, which translated to their superior anti-angiogenic activities. Taken together, a novel bestatin-SAHA hybrid was developed, which worked as a potent APN and HDAC dual inhibitor instead of a PROTAC.

Synthesis, molecular modeling, and biological evaluation of quinazoline derivatives containing the 1,3,4-oxadiazole scaffold as novel inhibitors of VEGFR2

RSC Advances ◽  
2015 ◽  
Vol 5 (26) ◽  
pp. 19914-19923 ◽  
Author(s):  
Fang Qiao ◽  
Yong Yin ◽  
Yu-Ning Shen ◽  
She-Feng Wang ◽  
Shao Sha ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Inhibitory Activity ◽  
Anticancer Agent ◽  
Biological Evaluation ◽  
Quinazoline Derivatives ◽  
Inhibitory Activities ◽  
Potent Inhibitory Activity ◽  
Mcf 7

A series of 4-alkoxyquinazoline derivatives containing the 1,3,4-oxadiazole scaffold were designed and synthesized. Their inhibitory activities were tested against A549, MCF-7 and Hela. 4j showed the most potent inhibitory activity and may be a potential anticancer agent.

Cholinesterase Inhibitory Activities of Selected Halogenated Thiophene Chalcones

2019 ◽  
Vol 19 (1) ◽  
pp. 67-71 ◽  
Author(s):  
Della G.T. Parambi ◽  
Fakhrya Aljoufi ◽  
Vikneswaran Murugaiyah ◽  
Githa E. Mathew ◽  
Sanal Dev ◽  
...  
Keyword(s):  
Monoamine Oxidase ◽  
Inhibitory Activity ◽  
Target Therapy ◽  
Monoamine Oxidase B ◽  
Inhibitory Ability ◽  
Ache Inhibitory Activity ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
Che Inhibitors ◽  
Potent Inhibitory Activity

Background: Dual-acting human monoamine oxidase B (hMAO-B) and cholinesterase (ChE) inhibitors are more effective than the classic one-drug one-target therapy for Alzheimer’s disease (AD). Methods: The ChE inhibitory ability of some halogenated thiophene chalcone-based molecules known to be selective hMAO-B inhibitors was evaluated. Results: Based on the IC50 values, the selected compounds were found to moderately inhibit ChE, with IC50 values in the range of 14-70 µM. Among the synthesised molecules, T8 and T6 showed the most potent inhibitory activity against AChE and BChE, respectively. Conclusion: Taken together, the data revealed that T8 could be further optimized to enhance its AChE inhibitory activity.

scholarly journals Health-Beneficial Phenolic Aldehyde inAntigonon leptopusTea

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Vanisree Mulabagal ◽  
Ruby L. Alexander-Lindo ◽  
David L. DeWitt ◽  
Muraleedharan G. Nair
Keyword(s):  
Lipid Peroxidation ◽  
Pain Relief ◽  
Inhibitory Activity ◽  
Inhibitory Concentration ◽  
Aerial Parts ◽  
Bioassay Guided Fractionation ◽  
Inhibitory Activities ◽  
Cox 2 ◽  
Dried Extract ◽  
Cox 1

Tea prepared from the aerial parts ofAntigonon leptopusis used as a remedy for cold and pain relief in many countries. In this study,A. leptopustea, prepared from the dried aerial parts, was evaluated for lipid peroxidation (LPO) and cyclooxygenase (COX-1 and COX-2) enzyme inhibitory activities. The tea as a dried extract inhibited LPO, COX-1 and COX-2 enzymes by 78%, 38% and 89%, respectively, at 100 g/mL. Bioassay-guided fractionation of the extract yielded a selective COX-2 enzyme inhibitory phenolic aldehyde, 2,3,4-trihydroxy benzaldehyde. Also, it showed LPO inhibitory activity by 68.3% at 6.25 g/mL. Therefore, we have studied other hydroxy benzaldehydes and their methoxy analogs for LPO, COX-1 and COX-2 enzymes inhibitory activities and found that compound1gave the highest COX-2 enzyme inhibitory activity as indicated by a 50% inhibitory concentration (IC50) at 9.7 g/mL. The analogs showed only marginal LPO activity at 6.25 g/mL. The hydroxy analogs6,7and9showed 55%, 61% and 43% of COX-2 inhibition at 100 g/mL. However, hydroxy benzaldehydes3and12showed selective COX-1 inhibition while compounds4and10gave little or no COX-2 enzyme inhibition at 100 g/mL. At the same concentration, compounds14,21and22inhibited COX-1 by 83, 85 and 70%, respectively. Similarly, compounds18,19and23inhibited COX-2 by 68%, 72% and 70%, at 100 g/mL. This is the first report on the isolation of compound1fromA. leptopustea with selective COX-2 enzyme and LPO inhibitory activities.

New Ferrocene Compounds as Selective Cyclooxygenase (COX-2) Inhibitors: Design, Synthesis, Cytotoxicity and Enzyme-inhibitory Activity

2018 ◽  
Vol 18 (2) ◽  
pp. 295-301 ◽  
Author(s):  
Shabnam Farzaneh ◽  
Elnaz Zeinalzadeh ◽  
Bahram Daraei ◽  
Soraya Shahhosseini ◽  
Afshin Zarghi
Keyword(s):  
Cell Lines ◽  
Inhibitory Activity ◽  
Fibroblast Cell ◽  
Breast Cancer Cell Lines ◽  
Ferrocene Derivatives ◽  
Cox 2 ◽  
Cytotoxicity Effects ◽  
Cox 2 Inhibitors ◽  
Mcf 7

Background: Due to the astonishing properties of ferrocene and its derivatives, it has a broad application in diverse areas. Numerous ferrocene derivatives demonstrated anti-proliferative activity. Also COX-2, as a key isoenzyme for production of prostaglandins, is frequently overexpressed in various cancers. It is now recognized that COX-2 over expression promotes tumorigenic functions which can be suppressed by COX-2 inhibitors, a phenomenon useful for the preventing of tumor progression. The combination of COX-2 inhibitors with other anti-cancer or cancer prevention drugs may reduce their side effects in future cancer prevention and treatment. Objective: Owing to high anticancer potential of ferrocene derivatives and considerable COX-2 inhibitory and cytotoxicity effects of our previously synthesized chalcones, we decided to incorporate the ferrocenyl moiety into appropriate COX-2 inhibitor chalcone based scaffold, to evaluate COX-2 inhibitory activity as well as anticancer activities. Methods: Chalcones were synthesized via clasien-schmidt condensation of methylsulfonyl aldehyde and acetyl ferrocene. Further different amines with solvent free and ultra sound condition were reacted with chalcones to have different 1-ferrocenyl-3-amino carbonyl compounds. Docking study was carried out with Auto Dock vina software. All the newly-synthesized compounds were evaluated for their cyclooxygenase-2 (COX-2) inhibitory activity using chemiluminescent enzyme assays as well as cytotoxicity activity against MCF-7 and T47D and fibroblast cell lines by MTT assay. Results: In vitro COX-1/COX-2 inhibition studies demonstrated that all compounds were selective inhibitors of the COX-2 isozyme with IC50 values in the highly potent 0.05-0.12 µM range, and COX-2 selectivity indexes (SI) in the 148.3-313.7 range. These results indicated that either potency or selectivity of COX-2 inhibitory activity was affected by the nature and size of the substituents on C-3 of propane-1-one. Also anti-proliferative and toxicity activities of synthesized compounds against breast cancer cell lines MCF-7 and T47D and fibroblast cell lines showed that the synthesized compounds had mild to moderate cytotoxicity against MCT7 and T47D breast cancer cell lines at 10 µM concentration. In vitro COX-1/COX-2 inhibition studies and anticancer activity against MCF-7, identified 1-ferrocenyl-3-(4-methylsulfonylphenyl) propen-1-one as a potent compound (IC50 COX-2 = 0.05 µM, MCF-7: % inhibition (at concentration of 10 µM) = 32.7%), and also 1-ferrocenyl-3- (propan-1-amine)-3-(4-methylsulfonylphenyl) propan-1-one showed the most selectivity on COX-2 inhibition (selectivity index= 313.7). Conclusion: A novel group of ferrocene compounds, possessing a methyl sulfonyl COX-2 pharmacophore were synthesized to investigate the effect of different substituents on selectivity and potency of COX-2 inhibitory activity and their cytotoxicity effects. This study indicates that 1-ferrocenyl-3-amino carbonyl compounds having ferrocene motif and methyl sulfonyl COX-2 pharmacophore is a suitable scaffold to design COX-2 inhibitors and anti-cancer agents.

scholarly journals Massiliamide, a cyclic tetrapeptide with potent tyrosinase inhibitory properties from the Gram-negative bacterium Massilia albidiflava DSM 17472T

2020 ◽  
Author(s):  
Andri Frediansyah ◽  
Jan Straetener ◽  
Heike Brötz-Oesterhelt ◽  
Harald Gross
Keyword(s):  
Absolute Configuration ◽  
Inhibitory Activity ◽  
Liquid Culture ◽  
Spectroscopic Analysis ◽  
2D Nmr ◽  
Negative Bacterium ◽  
Gram Negative ◽  
The Absolute ◽  
Potent Inhibitory Activity ◽  
Cyclic Tetrapeptide

AbstractA cyclic tetrapeptide, designated massiliamide, was isolated from the liquid culture of the Gram-negative bacterium Massilia albidiflava DSM 17472T. The structure was elucidated through extensive spectroscopic analysis, including HR-MS and 1D and 2D NMR experiments. The absolute configuration was determined using the Marfey´s method. Massiliamide showed potent inhibitory activity towards tyrosinase with an IC50 value of 1.15 µM and no cytotoxicity.

scholarly journals Deciphering the Role of π-Interactions in Polyelectrolyte Complexes Using Rationally Designed Peptides

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2074
Author(s):  
Sara Tabandeh ◽  
Cristina Elisabeth Lemus ◽  
Lorraine Leon
Keyword(s):  
Hydrogen Bonding ◽  
Phase Separation ◽  
Liquid Phase ◽  
Charge Density ◽  
Secondary Structures ◽  
Liquid Phase Separation ◽  
Polyelectrolyte Complexes ◽  
Π Interactions ◽  
Liquid Liquid Phase Separation

Electrostatic interactions, and specifically π-interactions play a significant role in the liquid-liquid phase separation of proteins and formation of membraneless organelles/or biological condensates. Sequence patterning of peptides allows creating protein-like structures and controlling the chemistry and interactions of the mimetic molecules. A library of oppositely charged polypeptides was designed and synthesized to investigate the role of π-interactions on phase separation and secondary structures of polyelectrolyte complexes. Phenylalanine was chosen as the π-containing residue and was used together with lysine or glutamic acid in the design of positively or negatively charged sequences. The effect of charge density and also the substitution of fluorine on the phenylalanine ring, known to disrupt π-interactions, were investigated. Characterization analysis using MALDI-TOF mass spectroscopy, H NMR, and circular dichroism (CD) confirmed the molecular structure and chiral pattern of peptide sequences. Despite an alternating sequence of chirality previously shown to promote liquid-liquid phase separation, complexes appeared as solid precipitates, suggesting strong interactions between the sequence pairs. The secondary structures of sequence pairs showed the formation of hydrogen-bonded structures with a β-sheet signal in FTIR spectroscopy. The presence of fluorine decreased hydrogen bonding due to its inhibitory effect on π-interactions. π-interactions resulted in enhanced stability of complexes against salt, and higher critical salt concentrations for complexes with more π-containing amino acids. Furthermore, UV-vis spectroscopy showed that sequences containing π-interactions and increased charge density encapsulated a small charged molecule with π-bonds with high efficiency. These findings highlight the interplay between ionic, hydrophobic, hydrogen bonding, and π-interactions in polyelectrolyte complex formation and enhance our understanding of phase separation phenomena in protein-like structures.

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