Binding mode analyses and pharmacophore model development for sulfonamide chalcone derivatives, a new class of α-glucosidase inhibitors

Bharatham, Kavitha; Bharatham, Nagakumar; Park, Ki Hun; Lee, Keun Woo

doi:10.1016/j.jmgm.2007.11.002

Cited by 108 publications

(74 citation statements)

References 34 publications

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“…Moreover, structurebased pharmacophore models with optimized features, for example the hydrogen-bonding and hydrophobic groups, could be applied to effectively select promising ligands in virtual screening. The most principal tools for virtual screening is structure-based docking [66][67][68], which optimally positions a virtual library of potential compounds in the pocket and scores for potential activity by using some popular docking programs, such as DOCK, AutoDock, FlexX, Glide and GOLD etc. Typically, the transition states or the transition state mimic structures of the inhibitor are employed in structure-based docking studies owing to good binding and the activation energies [33].…”

Section: Computer-aided Approachesmentioning

confidence: 99%

Investigation of Family 18 Chitinases and Inhibitors by Computer-Aided Approaches

Chu

Wang²,

Shen³

et al. 2012

CDT

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Chitinases belong to family 18 glycosyl hydrolases that can hydrolyze chitin by cleaving β-1,4-glycosidic bond, and are at key points in the life cycles of organism. The inhibitors of chitinases not only have chemotherapeutic potential against fungi, insects, but also hold anti-inflammatory efficacy against asthma and allergic disease in human. This review summarizes the structural characters of chitinases, the proposed catalytic mechanism, furthermore, also gives descriptions of currently existing inhibitors. In addition, computational studies of the interaction modes of chitinases with different inhibitors and substrates, as well as the inhibitor design of chitinases, are summarized so as to obtain an overall understanding for chitinases.Keywords: Chitinases, chitinase inhibitors, computer-aided approach. CHITIN AND CHITINASESChitin (C 8 H 13 O 5 N) n (shown in Fig. 1a), a linear insoluble homopolymer of N-acetyl-D-glucosamine (GlcNAc), is the second most abundant polysaccharide on the earth next to the cellulose [1, 2] and has been found in a wide range of organism, including bacteria, fungi, insects, and viruses [3][4][5].Accumulation of chitin in an organism is modulated by chitin synthase-mediated biosynthesis and chitinases-mediated hydrolytic degradation [6]. Since chitin synthases have become an ideal target for the development of pesticides and fugicides in agriculture, the design of chitin synthase's inhibitors has attracted much more attention [7,8]. Recently, some chitin synthase inhibitors have been successfully designed and synthesized in the group of Dr. Qing Yang [6,9], and these synthesized inhibitors were claimed to be novel potential agents due to their bioactivities. Chitinases (EC 3.2.1.14) play a key role in hydrolyzing β-1,4-glycosidic bond of the chitin into low molecular weight, soluble oligomers of GlcNAc [10,11]. Chitinases are currently classified into two different families of glycosyl hydrolases, namely family 18 and family 19 [12][13][14], and this review mainly focuses on family 18 chitinases studies, information available from their three-dimensional structures and the biochemistry of reaction. Chitinases are also widespread, and perform different functions in the different organism [15][16][17][18][19][20]. Although chitin does not exist in mammals, human chitinase family members, such as acidic mammalian chitinase (AMCase), have also been described in previous Therefore, the design of chitinases inhibitors is of great interest. The well-known inhibitor allosamidin (shown in Fig. 1b) is the most potent broad-spectrum inhibitor of chitinases. It inhibits chitinases by mimicing the reaction intermediate [24], but unfortunately, the synthesis of allosamidin and its derivatives are very difficult and expensive, which makes it a less suitable candidate targating a common chemotherapeutical therapy [25]. Izumida et al. found another effective chitinases inhibitor, the cyclic dipeptide [cyclo-(L-Arg-D-pro)] CI-4 (shown in Fig. 1c) [26]. CI-4 shows relatively weak inhibition ...

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Section: Computer-aided Approachesmentioning

confidence: 99%

Investigation of Family 18 Chitinases and Inhibitors by Computer-Aided Approaches

Chu

Wang²,

Shen³

et al. 2012

CDT

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“…This can be done by inhibiting the absorption of glucose through the inhibition of the carbohydrates hydrolyzed enzyme such as α-glucosidase and α-amylase [4]. The α -glucosidase is an enzyme that converts carbohydrates into glucose [5,6]. The mechanism of action α-glucosidase inhibitors  Corresponding author.…”

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confidence: 99%

“…Sulochrin (methyl 2-(2,6-dihydroxy-4-methylbenzoyl)-5-hydroxy-3-methoxybenzoate) isolated from Aspegillus terreus, showed its potency as an α-glucosidase inhibitor with IC 50 value 8.5 g/mL [10]. Sulochrin derivates, the methyl-4-hydroxy-5,7-diiodo-6-methoxy-6-methyl-3,4-dioxospiro [benzofuran-2(3H), 1- [2,5] cyclohexadiene]-2-carboxylate and methyl 5,7 dibromo-4-hydroxy-6-methoxy-6-methyl-3,4dioxospiro[benzofuran-2(3H), 1- [2,5] cyclohexdiene-2-carboxylate showed their glucose uptake activity in rat adiposite [11]. In silico field, α-glucosidase inhibitor interacted with α-glucosidase residues through formation of hydrogen bond.…”

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confidence: 99%

“…In silico field, α-glucosidase inhibitor interacted with α-glucosidase residues through formation of hydrogen bond. Derivates of sulfonamide interacted with Asp349, His348, Phe157, Tyr71, Phe177, Arg212 in α-glucosidase residues from Saccharomyces cerevisiae [5]. Derivatives of salacinol were also known as α-glucosidase inhibitors through interaction with Asp327, His600, Asp542, Asp203, Arg526 in NtMGAM residues [12].…”

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Synthesis of Sulochrin-<sup>125</sup>I and Its Binding Affinity as α-Glucosidase Inhibitor using Radioligand Binding Assay (RBA) Method

et al. 2014

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“…One study (Bharatham et al 2008) which utilized molecular docking software to model enzyme-ligand interactions suggests five pharmacophore features that are likely responsible for the binding between the alpha-glucosidase enzyme from Saccharomyces cerevisiae and inhibitory agents. These were identified as the presence of 3 hydrogenbond-acceptors (HBA), 1 hydrogen-bond donor (HBD), and 1 ring aromatic (RA).…”

Section: Digestive Enzyme Inhibition As Antidiabetic Actionmentioning

confidence: 99%

Medicinal Plants of Trinidad and Tobago: Selection of Antidiabetic Remedies

Bullard-Roberts¹

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Thanks to my Ethnobotany sisters, Cassy Quave and Janna Rose, for making the path smoother and to the Koptur lab for adopting me when I had no lab family left.Thanks to Sasha, Asha and Xtina from the Jaffe and Berry Labs at BBC for sharing their space, equipment and expertise.Thanks to James and Kate at the Quave Lab at Emory University for helping me to navigate through failed trials and strange calculations. Diabetes mellitus (DM) is a group of non-infectious diseases that cause hyperglycemia. DM symptoms were first clinically described by ancient Greek physicians whose prescriptions included plant-based remedies. Today, DM affects >400 million people globally and prevalence rates are rapidly increasing in developing countries where basic healthcare relies on local knowledge of botanical remedies. Many developing countries are home to diverse peoples and plants-providing fodder for varied plant-selection strategies and unique botanical pharmacopoeias.I addressed the plant-selection strategies used in a multi-ethnic, developing country, Trinidad and Tobago (T&T), to ascertain their role in shaping the local antidiabetic pharmacopoeia and to assess their benefits and risks in identifying safe and useful remedies. Using literature reviews, field surveys, and laboratory bioassays, Icompleted three categories of analysis.Ethnobotanical analyses showed that T&T's antidiabetic pharmacopoeia is primarily of recent origin as >50% of the 48 historical DM remedies were Neotropical natives, including congenerics of well-known medicinal Paleotropical genera. ix Nevertheless, conservative knowledge transmission was also evident as several Paleotropical species of T&T's pharmacopoeia, including Momordica charantia and Catharanthus roseus were also used in Africa, India and across the Caribbean.Paleotropical natives with a long history of use are likely to be safer remedies.Ethno-medicinal analyses of the pre-and post-2000 DM remedies of T&T, totaling 99 species, suggest that the centuries-old hot/cold folk disease-model was the model predominantly used in plant-selection. Parallels found between T&T folk concepts and biomedical mechanisms of DM provide probable bases for efficacy but the chronic use of purgatives and bitter-tasting plants is likely to be risky.Phytochemical analyses revealed that 69% of the tested plant extracts contained phenolic compounds, with more than half producing >80% alpha-glucosidase inhibition.Phenolic content and alpha-glucosidase inhibition were strongly correlated among food plants used as medicines, suggesting higher probability of selection as a result of nontarget effects. The medicinal use of food plants may provide the best margins of safety and efficacy in identifying antidiabetic remedies.Together, these analyses showed how culture-specific plant-selection strategies can identify safe, useful remedies for developing countries to address their increasing DM prevalence in a cost-effective and sustainable manner.x Table 3 Regions of the Indian sub-continent from which indentured laborers...

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Binding mode analyses and pharmacophore model development for sulfonamide chalcone derivatives, a new class of α-glucosidase inhibitors

Cited by 108 publications

References 34 publications

Investigation of Family 18 Chitinases and Inhibitors by Computer-Aided Approaches

Investigation of Family 18 Chitinases and Inhibitors by Computer-Aided Approaches

Synthesis of Sulochrin-<sup>125</sup>I and Its Binding Affinity as α-Glucosidase Inhibitor using Radioligand Binding Assay (RBA) Method

Medicinal Plants of Trinidad and Tobago: Selection of Antidiabetic Remedies

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