Synthesis, biological activities, and molecular docking studies of 2-mercaptobenzimidazole based derivatives

Ali, Mumtaz; Ali, Sardar; Khan, Momin; Rashid, Umer; Ahmad, Manzoor; Khan, Ajmal; Al‐Harrasi, Ahmed; Ullah, Farhat; Latif, Abdul

doi:10.1016/j.bioorg.2018.06.032

Cited by 47 publications

(37 citation statements)

References 17 publications

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“…Three-dimensional structure of porcine pancreatic α-amylase (PPA) complexed with acarbose was downloaded from Protein Data Bank (PDB code 1OSE). For α-glucosidase, docking studies were carried out on homology modelled α-glucosidase reported by our research group 35 . Preparation of ligands, downloaded enzymes, 3D protonation, energy minimization and determination of binding site was carried out by our previously reported methods 35,36 .…”

Section: Total Flavonoid Contents (Tfc)mentioning

confidence: 99%

“…For α-glucosidase, docking studies were carried out on homology modelled α-glucosidase reported by our research group 35 . Preparation of ligands, downloaded enzymes, 3D protonation, energy minimization and determination of binding site was carried out by our previously reported methods 35,36 . The view of the docking results and analysis of their surface with graphical representations were done using MOE and discovery studio visualizer 37 .…”

Section: Total Flavonoid Contents (Tfc)mentioning

confidence: 99%

“…Three-dimensional structure of porcine pancreatic α-amylase (PPA) complexed with acarbose was downloaded from Protein Data Bank (PDB code 1OSE). For α-glucosidase, docking studies were carried out on homology modelled α-glucosidase reported by our research group 35 . The binding energy data of the validation set for porcine pancreatic α-amylase is given in Table 3.…”

Section: Uhplc-q-tof-ms/ms Analysis Uhplc-qtof-ms/ms Was Used For Mementioning

confidence: 99%

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UHPLC-QTOF-MS/MS based phytochemical characterization and anti-hyperglycemic prospective of hydro-ethanolic leaf extract of Butea monosperma

Farooq

Mumtaz

Mukhtar

et al. 2020

Sci Rep

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Butea monosperma is one of the extensively used plants in traditional system of medicines for many therapeutic purposes. in this study, the antioxidant activity, α-glucosidase and α-amylase inhibition properties of freeze drying assisted ultrasonicated leaf extracts (hydro-ethanolic) of B. monosperma have been investigated. The findings revealed that 60% ethanolic fraction exhibited high phenolic contents, total flavonoid contents, highest antioxidant activity, and promising α-glucosidase and αamylase inhibitions. the UHpLc-Qtof-MS/MS analysis indicated the presence of notable metabolites of significant medicinal potential including apigenin, apigenin C-hexoside C-pentoside, apigenin Chexoside C-hexoside, apigenin-6,8-di-C-pentoside and genistin etc., in B. monosperma leave extract. Docking studies were carried out to determine the possible role of each phytochemical present in leaf extract. Binding affinity data and interaction pattern of all the possible phytochemicals in leaf extract of B. monosperma revealed that they can inhibit α-amylase and α-glucosidase synergistically to prevent hyperglycemia. Diabetes mellitus [DM] is most rapidly growing metabolic disorder in the world. It is primarily characterized by hyperglycemia which is associated with disturbed metabolism of carbohydrates, proteins and fats. Such metabolic dysfunctions at physiological level are known to cause detrimental health disorders which lead towards sickness and eventually death 1. According to WHO (World Health Organization), it is estimated that this chronic disease has affected nearly 150 million people throughout the world. This number will increase to three hundred million people or more up to 2025 2. The DM type II (DMT-II) is the most abundant form of diabetes and generally involves the phenomenon of insulin insensitivity or low insulin production. The main reasons behind the spread of this global health problem are mainly modern life style, obesity and consumption of high caloric diet. The growing rate of DM in Asian and African countries is two to three times more than the present rate in other countries 3. The role of reactive oxygen species (ROS) is very crucial in DMT-II pathogenesis. The ROS are produced because of electron transfer to oxygen from mitochondrial metabolic activity. The ROS are captured by antioxidants to maintain the redox homeostasis. However, over production or long-time exposure to ROS may create imbalance which further leads to state of oxidative stress. The oxidative stress exerts harmful impacts on bio-molecules to create metabolic dysfunction. The ROS under umbrella of oxidative stress disturbs the structure based activity of antioxidant enzymes to reduce the antioxidant potential of body 4. The ROS are also involved in impaired insulin secretion from pancreas probably due to dysfunction in β-cells 5. The elevated blood glucose level alters the normal functions of proteins through the process of glycation. The role of glycated end products is obvious in health deterioration and their long term existence...

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Section: Total Flavonoid Contents (Tfc)mentioning

confidence: 99%

Section: Total Flavonoid Contents (Tfc)mentioning

confidence: 99%

“…Three-dimensional structure of porcine pancreatic α-amylase (PPA) complexed with acarbose was downloaded from Protein Data Bank (PDB code 1OSE). For α-glucosidase, docking studies were carried out on homology modelled α-glucosidase reported by our research group 35 . The binding energy data of the validation set for porcine pancreatic α-amylase is given in Table 3.…”

Section: Uhplc-q-tof-ms/ms Analysis Uhplc-qtof-ms/ms Was Used For Mementioning

confidence: 99%

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UHPLC-QTOF-MS/MS based phytochemical characterization and anti-hyperglycemic prospective of hydro-ethanolic leaf extract of Butea monosperma

Farooq

Mumtaz

Mukhtar

et al. 2020

Sci Rep

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“…Molecular docking analysis was carried out using the software molecular docking analysis (MOE) and MOE 2018 was used, as reported by Ali et al (2018) . MOE is a licensed software system 1 designed by the Chemical Computing Group to support cheminformatics, molecular docking, bioinformatics, virtual screening, and structure-based-design and can be used to build new applications based on scientific vector language (SVL).…”

Section: Methodsmentioning

confidence: 99%

A Multi-Mode Bioactive Agent Isolated From Ficus microcarpa L. Fill. With Therapeutic Potential for Type 2 Diabetes Mellitus

et al. 2018

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Type 2 diabetes is a metabolic disorder, characterized by hyperglycemia and glucose intolerance. Natural products and its derived active compounds may be achievable alternatives for the treatment of type 2 diabetes. In present study we investigated the antidiabetic potential of Ficus microcarpa and isolated bioactive compounds i.e., Plectranthoic acid A (PA-A) and 3,4,5,7-Flavantetrol (FL). Anti-hyperglycemic potential was evaluated via α-glucosidase, α-amylase and dipeptidyl peptidase 4 (DPP-4) assays. 5’AMP-activated kinase (AMPK) activation potential was assessed by using primary hepatocytes. Distribution of PA-A in different parts of Ficus microcarpa was evaluated by using rapid high-performance liquid chromatography (HPLC). Ethyl acetate fraction (FME) exhibited significant inhibition of α-glucosidase, α-amylase, and DPP-4, therefore, was selected for isolation of bioactive compounds. Among isolated compounds PA-A was more potent and possessed pleotropic inhibitory activity with IC50 values of 39.5, 55.5, and 51.4 μM against α-glucosidase, α-amylase, and DPP-4, respectively. Our results showed that PA-A is also a potent activator of AMPK which is a central hub of metabolic regulation. Molecular docking studies confirmed the activity of PA-A against α-glucosidase, α-amylase, and DPP-4. Rapid HPLC method revealed that maximum concentration of PA-A is present in the stem (2.25 μg/mg dry weight) of Ficus microcarpa. Both in vitro and in silico studies proposed that Ficus microcarpa and its isolated compound PA-A could be an important natural source for alleviating the symptoms of type 2 diabetes mellitus and we suggest that PA-A should be explored further for its ultimate use for the treatment of type 2 diabetes.

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“…Validation of docking procedure was carried out by using re-dock method. Ligand and DNA/enzyme preparation, active site determination and docking procedure was carried out by using our previously reported procedures [3, 15]. The lowest energy minimized pose was used for further analysis.…”

Section: Methodsmentioning

confidence: 99%

Isolation of dihydrobenzofuran derivatives from ethnomedicinal species Polygonum barbatum as anticancer compounds

et al. 2019

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BackgroundEthnomedicinally, the family Polygonaceae is famous for the management of cancer. Various species of this family have been reported with anticancer potentials. This study was designed to isolate anticancer compounds from ethnomedicinally important species Polygonum barbatum.MethodsThe column chromatography was used for the isolation of compounds from the solvent fraction of P. barbatum. The characterization of isolated compounds was performed by various spectroscopic techniques like UV, IR, mass spectrometry and 1D-2D NMR spectroscopy. Keeping in view the ethnomedicinal importance of the family, genus and species of P. barbatum, the isolated compounds (1–3) were screened for anticancer potentials against oral cancer (CAL-27) and lungs cancer (NCI H460) cell lines using MTT assay. Active compound was further investigated for apoptosis by using morphological changes and flow cytometry analysis. In vivo anti-angiogenic study of the isolated compounds was also carried using chorioallantoic membrane assay. Docking studies were carried out to explore the mechanism of anticancer activity.ResultsThree dihydrobenzofuran derivatives (1–3) have been isolated from the ethyl acetate fraction of P. barbatum. The structures of isolated compounds were elucidated as methyl (2S,3S)-2-(3,4-dimethoxyphenyl)-4-((E)-3-ethoxy-3-oxoprop-1-en-1-yl)-7-methoxy-2,3-dihydrobenzo-furan-3-carboxylate (1), (E)-3-((2S,3S)-2-(3,4-dimethoxyphenyl)-7-methoxy-3-(methoxy carbonyl)-2,3-dihydrobenzofuran-4-yl)acrylic acid (2) and (2S,3S)-4-((E)-2-carboxyvinyl)-2-(3,4-dimethoxyphenyl)-7-hydroxy-2,3-dihydrobenzofuran-3-carboxylic acid (3). The compound 1 was found to be more potent with IC50 of 48.52 ± 0.95 and 53.24 ± 1.49 against oral cancer cells as compared to standard drug (IC50 = 97.76 ± 3.44 μM). Both compound also inhibited lung cancer cells but at higher concentrations. Morphological and flow cytometry analysis further confirms that compound 1 induces apoptosis after 24 to 48 h treatment. In antiangiogenesis assay, compounds 1, 2 and 3 exhibited IC50 values of 8.2 ± 1.1, 13.4 ± 1.1 and 57.7 ± 0.3 μM respectively. The docking studies revealed that the compounds under study have the potential to target the DNA and thymidylate synthase (TS).ConclusionBased on its overwhelming potency against the tested cell lines and in angiogenesis assay, compound 1 can be further evaluated mechanistically and can be developed as anticancer drug candidate.Electronic supplementary materialThe online version of this article (10.1186/s40659-018-0209-0) contains supplementary material, which is available to authorized users.

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Synthesis, biological activities, and molecular docking studies of 2-mercaptobenzimidazole based derivatives

Cited by 47 publications

References 17 publications

UHPLC-QTOF-MS/MS based phytochemical characterization and anti-hyperglycemic prospective of hydro-ethanolic leaf extract of Butea monosperma

UHPLC-QTOF-MS/MS based phytochemical characterization and anti-hyperglycemic prospective of hydro-ethanolic leaf extract of Butea monosperma

A Multi-Mode Bioactive Agent Isolated From Ficus microcarpa L. Fill. With Therapeutic Potential for Type 2 Diabetes Mellitus

Isolation of dihydrobenzofuran derivatives from ethnomedicinal species Polygonum barbatum as anticancer compounds

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