scholarly journals Design, Synthesis, and Evaluation of Acetylcholinesterase and Butyrylcholinesterase Dual-Target Inhibitors against Alzheimer’s Diseases

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 489
Author(s):  
Yan Guo ◽  
Hongyu Yang ◽  
Zhongwei Huang ◽  
Sen Tian ◽  
Qihang Li ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Inhibition Kinetics ◽  
Anionic Site ◽  
Design Synthesis ◽  
Potential Safety ◽  
Catalytic Sites ◽  
Enzyme Inhibition Kinetics ◽  
Molecular Modeling Studies ◽  
Inhibitory Activities

A series of novel compounds 6a–h, 8i–1, 10s–v, and 16a–d were synthesized and evaluated, together with the known analogs 11a–f, for their inhibitory activities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The inhibitory activities of AChE and BChE were evaluated in vitro by Ellman method. The results show that some compounds have good inhibitory activity against AChE and BChE. Among them, compound 8i showed the strongest inhibitory effect on both AChE (eeAChE IC50 = 0.39 μM) and BChE (eqBChE IC50 = 0.28 μM). Enzyme inhibition kinetics and molecular modeling studies have shown that compound 8i bind simultaneously to the peripheral anionic site (PAS) and the catalytic sites (CAS) of AChE and BChE. In addition, the cytotoxicity of compound 8i is lower than that of Tacrine, indicating its potential safety as anti-Alzheimer’s disease (anti-AD) agents. In summary, these data suggest that compound 8i is a promising multipotent agent for the treatment of AD.

scholarly journals Design, synthesis, biological evaluation, and molecular modeling studies of pyrazole-benzofuran hybrids as new α-glucosidase inhibitor

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fateme Azimi ◽  
Homa Azizian ◽  
Mohammad Najafi ◽  
Ghadamali Khodarahmi ◽  
Lotfollah Saghaei ◽  
...  
Keyword(s):  
Active Site ◽  
Inhibitory Effect ◽  
Biological Evaluation ◽  
Back Side ◽  
Binding Interaction ◽  
Dynamic Simulations ◽  
Design Synthesis ◽  
Standard Drug ◽  
Molecular Modeling Studies

AbstractIn this work, new derivatives of biphenyl pyrazole-benzofuran hybrids were designed, synthesized and evaluated in vitro through enzymatic assay for inhibitory effect against α-glucosidase activity. Newly identified inhibitors were found to be four to eighteen folds more active with IC50 values in the range of 40.6 ± 0.2–164.3 ± 1.8 µM, as compared to the standard drug acarbose (IC50 = 750.0 ± 10.0 μM). Limited Structure-activity relationship was established. A kinetic binding study indicated that most active compound 8e acted as the competitive inhibitors of α-glucosidase with Ki = 38 μM. Molecular docking has also been performed to find the interaction modes responsible for the desired inhibitory activity. As expected, all pharmacophoric features, used in the design of the hybrid, are involved in the interaction with the active site of the enzyme. In addition, molecular dynamic simulations showed compound 8e oriented vertically into the active site from mouth to the bottom and stabilized the enzyme domains by interacting with the interface of domain A and domain B and the back side of the active site while acarbose formed non-binding interaction with the residue belong to the domain A of the enzyme.

scholarly journals Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fariba Peytam ◽  
Ghazaleh Takalloobanafshi ◽  
Toktam Saadattalab ◽  
Maryam Norouzbahari ◽  
Zahra Emamgholipour ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Rat Small Intestine ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Mild Conditions ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

scholarly journals In Vitro α-Glucosidase and α-Amylase Inhibitory Activities of Free and Bound Phenolic Extracts from the Bran and Kernel Fractions of Five Sorghum Grain Genotypes

Foods ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1301
Author(s):  
Yun Xiong ◽  
Ken Ng ◽  
Pangzhen Zhang ◽  
Robyn Dorothy Warner ◽  
Shuibao Shen ◽  
...  
Keyword(s):  
Digestive System ◽  
Inhibitory Concentration ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Phenolic Contents ◽  
Inhibitory Activities ◽  
Sorghum Grain ◽  
Global Health Challenge ◽  
Phenolic Extracts

Diabetes is a global health challenge. Currently, an effective treatment for diabetes is to reduce the postprandial hyperglycaemia by inhibiting the carbohydrate hydrolysing enzymes in the digestive system. In this study, we investigated the in vitro α-glucosidase and α-amylase inhibitory effects of free and bound phenolic extracts, from the bran and kernel fractions of five sorghum grain genotypes. The results showed that the inhibitory effect of sorghum phenolic extracts depended on the phenolic concentration and composition. Sorghum with higher phenolic contents generally had higher inhibitory activity. Among the tested extracts, the brown sorghum (IS131C)-bran-free extract (BR-bran-free, half-maximal inhibitory concentration (IC50) = 18 ± 11 mg sorghum/mL) showed the strongest inhibition against α-glucosidase which was comparable to that of acarbose (IC50 = 1.39 ± 0.23 mg acarbose/mL). The red sorghum (Mr-Buster)-kernel-bound extract (RM-kernel-bound, IC50 = 160 ± 12 mg sorghum/mL) was the most potent in inhibiting α-amylase but was much weaker compared to acarbose (IC50 = 0.50 ± 0.03 mg acarbose/mL).

Design, synthesis and antibacterial evaluation of ocotillol derivatives with polycyclic nitrogen-containing groups

2021 ◽  
Author(s):  
Yucheng Cao ◽  
Kaiyi Wang ◽  
Jiali Wang ◽  
Haoran Cheng ◽  
Mengxin Ma ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Multidrug Resistant ◽  
Inhibitory Effect ◽  
Resistant Bacteria ◽  
Design Synthesis ◽  
In Vitro Antibacterial Activity ◽  
Strong Inhibitory Effect ◽  
Hospital Acquired ◽  
Derivatives Of

Aim: With the increasing abuse of antibacterial drugs, multidrug-resistant bacteria have become a burden on human health and the healthcare system. To find alternative compounds effective against hospital-acquired methicillin-resistant Staphylococcus aureus (HA-MRSA), novel derivatives of ocotillol were synthesized. Methods & Results: Ocotillol derivatives with polycyclic nitrogen-containing groups were synthesized and evaluated for in vitro antibacterial activity. Compounds 36–39 exhibited potent antibacterial activity against hospital-acquired MRSA, with MIC = 8–64 μg/ml. Additionally, a combination of compound 37 and the commercially available antibiotic kanamycin showed synergistic inhibitory effects, with a fractional inhibitory concentration index of ≤0.375. Conclusion: Compound 37 has a strong inhibitory effect, and this derivative has potential for use as a pharmacological tool to explore antibacterial mechanisms.

Longan seed polyphenols inhibit α-amylase activity and reduce postprandial glycemic response in mice

2021 ◽  
Author(s):  
Ting He ◽  
lei zhao ◽  
Yan Chen ◽  
Xin Zhang ◽  
Zhuoyan Hu ◽  
...  
Keyword(s):  
Enzyme Inhibition ◽  
Amylase Activity ◽  
Glycemic Response ◽  
Inhibition Assay ◽  
Inhibition Kinetics ◽  
Enzyme Inhibition Kinetics ◽  
Longan Seed ◽  
Kinetics Of

The effects of longan seed polyphenols (LSPs) on postprandial glycemic response in mice were investigated, enzyme inhibition kinetics of LSPs against α-amylase were studied using an inhibition assay in vitro,...

scholarly journals Design, synthesis and evaluation of belinostat analogs as histone deacetylase inhibitors

2019 ◽  
Vol 11 (21) ◽  
pp. 2765-2778
Author(s):  
Jie-Huan Zhang ◽  
Madhusoodanan Mottamal ◽  
Hai-Shan Jin ◽  
Shanchun Guo ◽  
Yan Gu ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Active Compound ◽  
Histone Deacetylase Inhibitors ◽  
Hdac Inhibitors ◽  
Antitumor Therapy ◽  
Design Synthesis ◽  
Inhibitory Activities ◽  
Antiproliferative Activities

Aim: Histone deacetylase (HDAC) is an attractive target for antitumor therapy. Therefore, the development of novel HDAC inhibitors is warranted. Materials & methods: A series of HDAC inhibitors based on N-hydroxycinnamamide fragment was designed as the clinically used belinostat analog using amide as the connecting unit. All target compounds were evaluated for their in vitro HDAC inhibitory activities and some selected compounds were tested for their antiproliferative activities. Conclusion: Among them, compound 7e showed an IC50 value of 11.5 nM in inhibiting the HDAC in a pan-HDAC assay, being the most active compound of the series.

scholarly journals Design, synthesis, molecular modelling and in vitro screening of monoamine oxidase inhibitory activities of novel quinazolyl hydrazine derivatives

2020 ◽  
Vol 7 (4) ◽  
pp. 200050
Author(s):  
Adel Amer ◽  
Abdelrahman H. Hegazi ◽  
Mohammed Khalil Alshekh ◽  
Hany E. A. Ahmed ◽  
Saied M. Soliman ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Monoamine Oxidase ◽  
In Vitro Screening ◽  
Phenyl Substituent ◽  
Design Synthesis ◽  
Mao B ◽  
Mao A ◽  
Ft Ir ◽  
Inhibitory Activities

A new series of N'-substituted benzylidene-2-(4-oxo-2-phenyl-1,4-dihydroquinazolin-3(2H)-yl)acetohydrazide ( 5a–5h ) has been synthesized, characterized by FT-IR, NMR spectroscopy and mass spectrometry and tested against human monoamine oxidase (MAO) A and B. Only (4-hydroxy-3-methoxybenzylidene) substituted compounds gave submicromolar inhibition of MAO-A and MAO-B. Changing the phenyl substituent to methyl on the unsaturated quinazoline ring ( 12a–12d ) decreased inhibition, but a less flexible linker ( 14a–14d ) resulted in selective micromolar inhibition of hMAO-B providing insight for ongoing design.

Design, synthesis, and biological evaluation of new series of 2-amido-1,3,4-thiadiazole derivatives as cytotoxic agents

2016 ◽  
Vol 71 (3) ◽  
pp. 205-210 ◽  
Author(s):  
Ali Almasirad ◽  
Loghman Firoozpour ◽  
Maliheh Nejati ◽  
Najmeh Edraki ◽  
Omidreza Firuzi ◽  
...  
Keyword(s):  
Human Tumor ◽  
Inhibitory Effect ◽  
Biological Evaluation ◽  
Cytotoxic Agents ◽  
Antitumor Activities ◽  
Design Synthesis ◽  
Ethidium Bromide Staining ◽  
Thiadiazole Derivatives ◽  
Synthesis And Biological Evaluation

AbstractA series of novel 1,3,4-thiadiazole derivatives bearing an amide moiety were designed, synthesized, and evaluated for their in vitro antitumor activities against HL-60, SKOV-3 and MOLT-4 human tumor cell lines by MTT assay. Ethyl 2-((5-(4-methoxybenzamido)-1,3,4-thiadiazol-2-yl)thio)acetate (5f) showed the best inhibitory effect against SKOV-3 cells, with an IC50 value of 19.5 μm. In addition, the acridine orange/ethidium bromide staining assay in SKOV-3 cells suggested that the cytotoxic activity of 5f occurs via apoptosis.

Synthesis and in vitro evaluation of substituted aryl- and hetarylmethyl phosphonate and phosphate — UMP derivatives as potential glucosyltransferase inhibitors

2002 ◽  
Vol 80 (8) ◽  
pp. 973-982 ◽  
Author(s):  
Asish K Bhattacharya ◽  
Florian Stolz ◽  
Jürgen Kurzeck ◽  
Wolfgang Rüger ◽  
Richard R Schmidt
Keyword(s):  
Transition State ◽  
Enzyme Inhibitors ◽  
Future Generations ◽  
Arbuzov Reaction ◽  
Inhibition Kinetics ◽  
Design Synthesis ◽  
Double Stranded Dna ◽  
Structure Activity ◽  
Potential Inhibitors

The enzyme β (1[Formula: see text]4)-glucosyltransferase (BGT) catalyses the transfer of glucose from uridine diphosphoglucose (UDP-Glc) to 5-hydroxymethylcytosine (5-HMC) bases in double-stranded DNA. Potential inhibitors of BGT were developed by structure-based design and synthesized. The designed inhibitors 1–6 provide conformational mimicry of the transition state in glucosyltransfer reactions. The key synthetic steps involve a Michaelis–Arbuzov reaction followed by coupling with uridine-5'-morpholidophosphate as activated UMP derivative. The compounds were tested for in vitro inhibitory activity against BGT and the inhibition kinetics were examined. Three of the designed molecules were found to be potential inhibitors of BGT having IC50 values in the micromolar (µM) range. Useful structure–activity relationships were established which provide guidelines for the design of future generations of inhibitors of BGT.Key words: β-glucosyltransferase, transition state, enzyme inhibitors, structure-based design, synthesis.

scholarly journals IN VITRO ANTIDIABETIC POTENTIALS OF SIDA ACUTA, ABUTILON INDICUM AND MALVASTRUM COROMANDELIANUM

2020 ◽  
pp. 87-89
Author(s):  
NANTAPORN DINLAKANONT ◽  
CHANIDA PALANUVEJ ◽  
NIJSIRI RUANGRUNGSI
Keyword(s):  
Enzyme Inhibitors ◽  
Postprandial Glucose ◽  
Inhibitory Effect ◽  
Glucose Absorption ◽  
Alpha Amylase ◽  
Sida Acuta ◽  
Inhibitory Activities ◽  
Alpha Glucosidase ◽  
Abutilon Indicum

Objective: Starch metabolizing enzyme inhibitors are able to retard postprandial glucose absorption. This study aimed to investigate the in vitro inhibitory activities of alpha-glucosidase and alpha-amylase of three Malvaceous weeds i.e. Sidaacuta Burm. f., Abutilon indicum (Linn.) Sweet and Malvastrumcoromandelianum (Linn.) Garcke. Methods: The stems, roots and leaves of S. acuta, A. indicum and M. coromandelianum were sequentially extracted in dichloromethane and methanol, respectively. All fractions were tested for the inhibitory activities on yeast alpha-glucosidase, rat intestinal alpha-glucosidase and porcine alpha-amylase. p-Nitrophenyl-α-D-glucopyranoside and 2-chloro-4 nitrophenol-α-D- maltotrioside were used as the substrate for glucosidase and amylase respectively. Results: The dichloromethane fraction of the roots and stems from A. indicum and dichloromethane as well as methanolic fractions of the stems of M. coromandelianum could inhibit yeast alpha-glucosidase compared to 1-deoxynojirimycin with the IC50 of 0.36, 0.45, 0.48, 0.48 and 0.58 mg/ml respectively. A. indicum root methanolic fraction had the highest inhibitory effect on rat alpha-glucosidase activity compared to 1-deoxynojirimycin with the IC50 of 0.08 and 0.11 mg/ml respectively. M. coromandelianum, the dichloromethane fraction of roots and the methanolic fraction of stems, showed the strongest effect on alpha-amylase inhibition compared to acarbose with the IC50 of 0.07, 0.07 and 2.7 mg/ml, respectively. Conclusion: S. acuta, A. indicum and M. coromandelianum dichloromethane and methanolic fractions of the root, stem and leaf parts demonstrated an appreciable inhibitory activity on alpha-amylase from porcine, alpha-glucosidase from Saccharomyces cerevisiae and from rat intestine compared to 1-deoxynojirimycin and acarbose.

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