Novel photochromic inhibitor for mitotic kinesin Eg5 which forms multiple isomerization states

2021 ◽  
Author(s):  
Islam Md Alrazi ◽  
Kei Sadakane ◽  
Shinsaku Maruta
Keyword(s):  
Inhibitory Activity ◽  
Molecular Motor ◽  
The Novel ◽  
Precise Control ◽  
Atpase Assay ◽  
Ic50 Value ◽  
Motor Activities ◽  
Ic50 Values ◽  
Kinesin Eg5 ◽  
Mitotic Kinesin Eg5

Abstract The mitotic kinesin Eg5 is a plus-end directed homotetrameric molecular motor essential for the formation of bipolar spindles during cell division. Kinesin Eg5 is overexpressed in cancer cells and hence considered as a target for cancer therapy; the inhibitors specific for Eg5 have been developed as anticancer drugs. In this study, we synthesized a novel functional photoresponsive inhibitor composed of spiropyran and azobenzene derivatives to control Eg5 function with multistage inhibitory activity accompanied by the formation of different isomerization states. The photochromic inhibitor spiropyran-sulfo-azobenzene (SPSAB) exhibited three isomerization states: spiro (SP)-trans, merocyanine (MC)-cis and MC-trans, upon exposure to visible light, ultraviolet and in the dark, respectively. SPSAB-induced reversible changes in the inhibitory activity of ATPase and motor activities correlating with photoisomerization among the three states. Among the three isomerization states of SPSAB, the SP-trans isomer showed potent inhibitory activity at an IC50 value of 30 µM in the basal ATPase assay. MC-trans and MC-cis exhibited less inhibitory activity at IC50 values of 38 and 86 µM, respectively. The results demonstrated that the novel photochromic inhibitor enabled precise control of Eg5 function at three different levels using light irradiation.

Inhibition of Protein Tyrosine Phosphatase 1B by Lutein Derivatives isolated from Mexican Oregano (Lippia graveolens)

2018 ◽  
Vol 17 (3) ◽  
pp. 134-139
Author(s):  
R.M. Perez-Gutierrez
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Inhibitory Activity ◽  
Spectroscopic Data ◽  
Methanol Extract ◽  
Tyrosine Phosphatase ◽  
Positive Control ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Ic50 Value ◽  
Ic50 Values

Methanol extract from Lippia graveolens (Mexican oregano) was studied in order to identify inhibitory bioactives for protein tyrosine phosphatase 1B (PTP1B). Known flavone as lutein (1), and another flavone glycoside such as lutein-7-o-glucoside (2), 6-hydroxy-lutein-7-ohexoside (3) and lutein-7-o-ramnoide (4) were isolated from methanol extract of aerial parts of the Lippia graveolens. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR, MS and compared with spectroscopic data previously reported. These flavones were evaluated for PTP1B inhibitory activity. Among them, compounds 1 and 3 displayed potential inhibitory activity against PTP1B with IC50 values of 7.01 ± 1.25 μg/ml and 18.4 μg/ml, respectively. In addition, compound 2 and 4 showed moderate inhibitory activity with an IC50 value of 23.8 ± 6.21 and 67.8 ± 5.80 μg/ml respectively. Among the four compounds, luteolin was found to be the most potent PTP1B inhibitor compared to the positive control ursolic acid, with an IC50 value of 8.12 ± 1.06 μg/ml. These results indicate that flavonoids constituents contained in Lippia graveolens can be considered as a natural source for the treatment of type 2 diabetes.

Inhibitory Activity of Extracts from Mycelia Materials of Several Mushrooms on the Angiotensin I-Converting Enzyme

2012 ◽  
Vol 610-613 ◽  
pp. 3541-3544
Author(s):  
Pei Sheng Yan ◽  
Xiu Jun Gao
Keyword(s):  
Liquid Medium ◽  
Inhibitory Activity ◽  
Water Extract ◽  
Angiotensin I ◽  
Water Extracts ◽  
Angiotensin I Converting Enzyme ◽  
Ic50 Value ◽  
Ic50 Values ◽  
The Difference ◽  
Ace Inhibitory

ACE inhibitory activities of water extracts from mycelia of 6 kinds of mushrooms in liquid fermentation were investigated. All strains cultivated in shaking flask containing liquid medium, and yield of mycelia ranged from 0.051 to 1.392 g mycelia/day/L liquid medium in average. Resulting mycelia were extracted with distilled water at 50°Cfor 200 min, and the yield of water extracts from mycelia ranged from 287.475 to 490.088 mg/g dried mycelia. These water extracts were used to assay their ACE inhibitory activity. Results showed that their IC50 values ranged from 1.277 to 5.250 mg/ml. The difference among IC50 values of these water extracts were significant (p<0.05 or p<0.001). Lactarius camphorates (IC50: 1.646±0.061mg/mL) was the specie which had relatively lower IC50 value than others, as well as relatively higher water extract yield. The results highlighted the potential for making antihypertensive functional foods or drugs from liquid cultured mycelia of Lactarius camphorates.

scholarly journals Study on α-glucosidase inhibitory activity of 40 kinds of vegetables, tubers, and fruits in An Giang

2021 ◽  
Vol 63 (4) ◽  
pp. 42-46
Author(s):  
Thi-My-Linh Lam ◽  
◽  
Minh-Tuan Le ◽  
Manh-Ha Bui ◽  
◽  
...  
Keyword(s):  
Glycine Max ◽  
Inhibitory Activity ◽  
Positive Control ◽  
Syzygium Cumini ◽  
Inhibition Rate ◽  
Ic50 Value ◽  
Areca Catechu ◽  
Ic50 Values

A study on the α-glucosidase inhibitory activity of 40 kinds of vegetables, tubers, and fruits found in the An Giang province was conducted. The results indicated that all 40 extracted samples displayed α-glucosidase inhibitory activity at a concentration of 250 μg ml-1, 36 extracted samples showed an inhibition rate greater than 50% at 250 μg ml-1, 25 extracted samples had over 50% at 100 μg ml-1, 17 extracted samples possessed more than 50% at 50 μg ml-1, 7 extracted samples sampled showed over 50% at 25 μg ml-1, 5 extracted samples were greater than 50% at 10 μg ml-1, and 1 extracted sample was greater than 50% at 1 μg ml-1. Among the 40 samples, those taken from the seeds of Areca catechu, the fruits of Cassia grandis, the fruits of Syzygium cumini, the seeds of Glycine max,andthe stems of Enydra fluctuansexhibited the strongest α-glucosidase inhibitory activity in methanol, with IC50 values of 0.15, 2.54, 4.05, 5.17 and 8.68 μg ml-1, respectively, which were stronger than the positive control acarbose with an IC50 value of 214.5 μg ml-1

scholarly journals Inhibition of Androgen Synthesis in Human Testicular and Prostatic Microsomes and in Male Rats by Novel Steroidal Compounds*

Endocrinology ◽  
1999 ◽  
Vol 140 (6) ◽  
pp. 2891-2897 ◽  
Author(s):  
Ivo P. Nnane ◽  
Katsuya Kato ◽  
Yang Liu ◽  
Brian J. Long ◽  
Qing Lu ◽  
...  
Keyword(s):  
Male Rats ◽  
Normal Male ◽  
Rat Tissues ◽  
The Novel ◽  
Androgen Synthesis ◽  
Potent Inhibition ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Wet Weight

Abstract The C17,20-lyase and 5α-reductase are key enzymes in the biosynthesis of androgens. The effects of novel steroidal compounds were evaluated as inhibitors against both human C17,20-lyase and 5α-reductase in vitro. The concentrations of testosterone (T) and dihydrotestosterone (DHT) in the prostate, testis and serum and changes in the tissue weights were also determined in rats treated with the novel inhibitors. L-12 and L-26 showed potent inhibition of human testicular C17,20-lyase with IC50 values of 50 and 25 nm, respectively. L-12, L-38, and I-47 showed moderate inhibition of human testicular C17,20-lyase with IC50 values of 75, 108, and 70 nm, respectively similar to ketoconazole (78 nm). Interestingly, L-6, L-26, and L-38 also showed some inhibitory activity against 5α-reductase with IC50 values of 75, 125, and 377 nm, respectively. Finasteride, an inhibitor of 5α-reductase had an IC50 value of 33 nm. However, ketoconazole did not inhibit 5α-reductase nor did finasteride inhibit C17,20-lyase. Treatment of normal male rats with several of these novel inhibitors (50 mg/kg·day, sc, for 14 consecutive days) caused about 45–91% decrease in serum, testicular and prostatic T concentration. Similarly, serum and prostatic DHT concentration were significantly decreased in rats treated with these novel compounds by 50–90% compared with controls. Surgical castration caused almost complete elimination of circulating T and DHT concentration in rat tissues. L-6 and L-12 were the most effective and reduced the wet weight of the prostate by 50%. Although future improvements in their bioavailability are necessary, these novel steroidal compounds show promise as potential agents for reducing T and DHT levels in patients with androgen dependent diseases.

scholarly journals Thioester-Containing Benzoate Derivatives with α-Glucosidase Inhibitory Activity from the Deep-Sea-Derived Fungus Talaromyces indigoticus FS688

Marine Drugs ◽  
2021 ◽  
Vol 20 (1) ◽  
pp. 33
Author(s):  
Mingqiong Li ◽  
Saini Li ◽  
Jinhua Hu ◽  
Xiaoxia Gao ◽  
Yanlin Wang ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Deep Sea ◽  
Spectroscopic Analysis ◽  
X Ray Diffraction ◽  
Docking Analysis ◽  
X Ray ◽  
Structure Activity ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Benzoate Derivatives

Eurothiocins C–H (1–6), six unusual thioester-containing benzoate derivatives, were isolated from the deep-sea-derived fungus Talaromyces indigoticus FS688 together with a known analogue eurothiocin A (7). Their structures were elucidated through spectroscopic analysis and the absolute configurations were determined by X-ray diffraction and ECD calculations. In addition, compound 1 exhibited significant inhibitory activity against α-glucosidase with an IC50 value of 5.4 μM, while compounds 4 and 5 showed moderate effects with IC50 values of 33.6 and 72.1 μM, respectively. A preliminary structure–activity relationship is discussed and a docking analysis was performed.

scholarly journals Halogen-Substituted Triazolethioacetamides as a Potent Skeleton for the Development of Metallo-β-Lactamase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1174 ◽  
Author(s):  
Yilin Zhang ◽  
Yong Yan ◽  
Lufan Liang ◽  
Jie Feng ◽  
Xuejun Wang ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Inhibitory Activity ◽  
Docking Studies ◽  
Hydroxyl Group ◽  
Inhibition Kinetics ◽  
Ic50 Value ◽  
Lactam Antibiotic ◽  
Value Range ◽  
Ic50 Values ◽  
Enzyme Inhibition Kinetics

Metallo-β-lactamases (MβLs) are the target enzymes of β-lactam antibiotic resistance, and there are no effective inhibitors against MβLs available for clinic so far. In this study, thirteen halogen-substituted triazolethioacetamides were designed and synthesized as a potent skeleton of MβLs inhibitors. All the compounds displayed inhibitory activity against ImiS with an IC50 value range of 0.032–15.64 μM except 7. The chlorine substituted compounds (1, 2 and 3) inhibited NDM-1 with an IC50 value of less than 0.96 μM, and the fluorine substituted 12 and 13 inhibited VIM-2 with IC50 values of 38.9 and 2.8 μM, respectively. However, none of the triazolethioacetamides exhibited activity against L1 at inhibitor concentrations of up to 1 mM. Enzyme inhibition kinetics revealed that 9 and 13 are mixed inhibitors for ImiS with Ki values of 0.074 and 0.27μM using imipenem as the substrate. Docking studies showed that 1 and 9, which have the highest inhibitory activity against ImiS, fit the binding site of CphA as a replacement of ImiS via stable interactions between the triazole group bridging ASP120 and hydroxyl group bridging ASN233.

Phosphodiesterase 5 Inhibitors from Derris scandens

Planta Medica ◽  
2018 ◽  
Vol 84 (15) ◽  
pp. 1134-1140 ◽  
Author(s):  
Nattiya Chaichamnong ◽  
Prapapan Temkitthawon ◽  
Nantaka Khorana ◽  
Prompan Pitpakdeeanan ◽  
Pornnarin Taepavarapruk ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Ethanol Extract ◽  
Bioactive Constituents ◽  
First Line ◽  
Phosphodiesterase 5 Inhibitors ◽  
Ic50 Value ◽  
Limit Of Quantitation ◽  
Satisfactory Precision ◽  
Ic50 Values ◽  
Phosphodiesterase 5

AbstractPhosphodiesterase 5 inhibitors have been used as a first-line medicine for the treatment of erectile dysfunction. In the search for new phosphodiesterase 5 inhibitors from natural sources, we found that the 95% ethanol extract of Derris scandens stem showed phosphodiesterase 5 inhibitory activity with an IC50 value of about 7 µg/mL. Seven isoflavones and a coumarin constituent isolated from this plant were investigated for phosphodiesterase 5 inhibitory activity. The results showed that osajin (8), 4′,5,7-trihydroxybiprenylisoflavone (4), and derrisisoflavone A (2) had the ability to inhibit phosphodiesterase 5 with IC50 values of 4, 8, and 9 µM, respectively. These compounds exhibited selectivity on phosphodiesterase 5 over phosphodiesterase 1, however, the selectivity on phosphodiesterase 5 over phosphodiesterase 6 was low. In order to quantitatively determine these bioactive constituents in D. scandens extract, LC-QTOF-MS method has been developed and validated. The limit of quantitation values in the range of 0.1 – 5 µg/mL were obtained. The assay showed satisfactory precision and accuracy. The results from our method showed that the 95% ethanol extract of D. scandens stem was comprised of all eight compounds, with derrisisoflavone A (2) and lupalbigenin (3) presenting as the major constituents.

Synthesis, in vitro Acetylcholinesterase Inhibitory Activity Evaluation and Docking Investigation of Some Aromatic Chalcones

MedPharmRes ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 15-25
Author(s):  
Dao Tran ◽  
Son Tran ◽  
Vi Nguyen ◽  
Tri Le ◽  
Minh Thai ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Condensation Reaction ◽  
Acetylcholinesterase Inhibitors ◽  
Docking Studies ◽  
Acetylcholinesterase Inhibitory Activity ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Inhibitory Activities ◽  
Ellman’S Method

In this study, a total of twenty chalcones were synthesized via Claisen-Schmidt condensation reaction and evaluated for their in vitro acetylcholinesterase inhibitory activities using Ellman’s method. Molecular docking studies on acetylcholinesterase were performed to elucidate the interactions between these chalcone derivatives and acetylcholinesterase active site at the molecular level. From the series, six compounds (S1-5 and S17) exhibited strong acetylcholinesterase inhibitory activities with IC50 values below 100 µM compared to the parent unsubstituted chalcone. Compound S17 (4’-amino-2-chlorochalcone) showed the strongest acetylcholinesterase inhibitory activity in the investigated group with IC50 value of 36.10 µM. Molecular modeling studies were consistent with the results of in vitro acetylcholinesterase inhibitory activities, and chalcone S17 could be considered as a potential lead compound for the development of new acetylcholinesterase inhibitors.

scholarly journals Discovery of 8-Amino-Substituted 2-Phenyl-2,7-Naphthyridinone Derivatives as New c-Kit/VEGFR-2 Kinase Inhibitors

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4461 ◽  
Author(s):  
Haiyan Sun ◽  
Linsheng Zhuo ◽  
Huan Dong ◽  
Wei Huang ◽  
Nengfang She
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
Kinase Inhibitors ◽  
Biological Screening ◽  
Binding Interactions ◽  
Lead Structure ◽  
Lead Compounds ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Insight Into

The 2,7-naphthyridone scaffold has been proposed as a novel lead structure of MET inhibitors by our group. To broaden the application of this new scaffold, a series of 8-amino-substituted 2-phenyl-2,7-naphthyridin-1(2H)-one derivatives were designed and synthesized. Preliminary biological screening resulted in the discovery of a new lead of c-Kit and VEGFR-2 kinase inhibitors. Compound 9k exhibited excellent c-Kit inhibitory activity, with an IC50 value of 8.5 nM, i.e., it is 38.8-fold more potent than compound 3 (IC50 of 329.6 nM). Moreover, the compounds 10l and 10r exhibited good VEGFR-2 inhibitory activity, with IC50 values of 56.5 and 31.7 nM, respectively, i.e., they are 5.0–8.8-fold more potent than compound 3 (IC50 of 279.9 nM). Molecular docking experiments provided further insight into the binding interactions of the new lead compounds with c-Kit and VEGFR-2 kinase. In this study, an 8-amino-substituted 2-phenyl-2,7-naphthyridin-1(2H)-one scaffold was identified as the new lead structure of c-Kit and VEGFR-2 kinase inhibitors.

Sign in / Sign up

Export Citation Format

Share Document