Design and synthesis of harzialactone analogues: Promising anticancer agents

Pawar, Vishwas U.; Ghosh, Sougata; Chopade, Balu A.; Shinde, Vaishali

doi:10.1016/j.bmcl.2010.10.100

Cited by 22 publications

(11 citation statements)

References 18 publications

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“…Computational docking studies provided immensely important information towards understanding the mechanism behind active site binding interactions [25], [26]. The salient feature of α-amylase is presence of three highly conserved and catalytic residues such as Asp197, Glu233 and Asp300 in the active site pocket [54].…”

Section: Discussionmentioning

confidence: 99%

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Diosgenin from Dioscorea bulbifera: Novel Hit for Treatment of Type II Diabetes Mellitus with Inhibitory Activity against α-Amylase and α-Glucosidase

et al. 2014

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Diabetes mellitus is a multifactorial metabolic disease characterized by post-prandial hyperglycemia (PPHG). α-amylase and α-glucosidase inhibitors aim to explore novel therapeutic agents. Herein we report the promises of Dioscorea bulbifera and its bioactive principle, diosgenin as novel α-amylase and α-glucosidase inhibitor. Among petroleum ether, ethyl acetate, methanol and 70% ethanol (v/v) extracts of bulbs of D. bulbifera, ethyl acetate extract showed highest inhibition upto 72.06 ± 0.51% and 82.64 ± 2.32% against α-amylase and α-glucosidase respectively. GC-TOF-MS analysis of ethyl acetate extract indicated presence of high diosgenin content. Diosgenin was isolated and identified by FTIR, 1H NMR and 13C NMR and confirmed by HPLC which showed an α-amylase and α-glucosidase inhibition upto 70.94 ± 1.24% and 81.71 ± 3.39%, respectively. Kinetic studies confirmed the uncompetitive mode of binding of diosgenin to α-amylase indicated by lowering of both Km and Vm. Interaction studies revealed the quenching of intrinsic fluorescence of α-amylase in presence of diosgenin. Similarly, circular dichroism spectrometry showed diminished negative humped peaks at 208 nm and 222 nm. Molecular docking indicated hydrogen bonding between carboxyl group of Asp300, while hydrophobic interactions between Tyr62, Trp58, Trp59, Val163, His305 and Gln63 residues of α-amylase. Diosgenin interacted with two catalytic residues (Asp352 and Glu411) from α-glucosidase. This is the first report of its kind that provides an intense scientific rationale for use of diosgenin as novel drug candidate for type II diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

“…FTIR was recorded on Shimazdu FTIR spectrometer. NMR spectra have been recorded with Varian 300 MHz spectrometer [24]–[26]. Pure bioactive sample was analyzed and compared with standard diosgenin by using Agilent Infinity series HPLC with eclipse C18 column (4.6 × 100 mm and 3.5 µm particle size).…”

Section: Methodsmentioning

confidence: 99%

Diosgenin from Dioscorea bulbifera: Novel Hit for Treatment of Type II Diabetes Mellitus with Inhibitory Activity against α-Amylase and α-Glucosidase

et al. 2014

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“…They are isolated from roots, tubers, knots, stalks, seeds and fruits [1,2,3] and have also been found in mushrooms and cyanobacteria [4,5]. They are reported to display a wide variety of biological activities such as anticancer [6,7], antioxidant [8,9], antifungal [10,11], antiviral [12,13], anti-inflammatory [14], antifeedant [15], anticonvulsant [16] and phytoestrogenic [17,18].…”

Section: Introductionmentioning

confidence: 99%

Chemoenzymatic Synthesis of trans-β-Aryl-δ-hydroxy-γ-lactones and Enzymatic Kinetic Resolution of Their Racemic Mixtures

et al. 2016

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Two novel and convenient routes to obtain enantiomerically enriched trans-β-aryl-δ-hydroxy-γ-lactones 5a-d with potential antifeedant and anticancer activity were developed. In the first method starting from corresponding enantiomers of γ,δ-unsaturated esters 4a-d derived from enzymatically resolved allyl alcohols 1a-d, both enantiomers of hydroxylactones 5a-d were synthesized with high enantiomeric excesses (73%-97%). Configurations of the stereogenic centers of the synthesized compounds were assigned based on the mechanism of acidic lactonization of esters 4a-d in the presence of m-chloroperbenzoic acid (m-CPBA). An alternative method for the production of optically active trans-β-aryl-δ-hydroxy-γ-lactones 5a-d was lipase-catalyzed kinetic resolution of their racemic mixtures by transesterification with vinyl propionate as the acyl donor. The most efficient enzyme in the screening procedure was lipase B from Candida antarctica. Its application on a preparative scale after 6 h afforded unreacted (+)-(4S,5R,6S)-hydroxylactones 5a-d and (+)-(4R,5S,6R)-propionates 6a-d, most of them with high enantiomeric excesses (92%-98%). Resolution of lactone 5d with bulky 1,3-benzodioxol ring provided products with significantly lower optical purity (ee = 89% and 84% for hydroxylactone 5d and propionate 6d, respectively). The elaborated methods give access to both enantiomers of trans-β-aryl-δ-hydroxy-γ-lactones 5a-d with the defined absolute configurations of stereogenic centers, which is crucial requirement for the investigations of relationship: spatial structure-biological activity.

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“…MCF7 was cultured in DMEM medium [35] while HL60 cells were cultured in a humidified atmosphere (37°C, 5% CO 2 ) in RPMI1640 medium supplemented with 10% fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

A Simple, Efficient Synthesis of 2-Aryl Benzimidazoles Using Silica Supported Periodic Acid Catalyst and Evaluation of Anticancer Activity

Sontakke

Ghosh

Lawande

et al. 2013

ISRN Organic Chemistry

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A new, efficient method for the synthesis of 2-aryl substituted benzimidazole by using silica supported periodic acid (H5IO6-SiO2) as a catalyst has been developed. The salient feature of the present method includes mild reaction condition, short reaction time, high yield and easy workup procedure. The synthesized benzimidazoles exhibited potent anticancer activity against MCF7 and HL60 cell lines.

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Design and synthesis of harzialactone analogues: Promising anticancer agents

Cited by 22 publications

References 18 publications

Diosgenin from Dioscorea bulbifera: Novel Hit for Treatment of Type II Diabetes Mellitus with Inhibitory Activity against α-Amylase and α-Glucosidase

Diosgenin from Dioscorea bulbifera: Novel Hit for Treatment of Type II Diabetes Mellitus with Inhibitory Activity against α-Amylase and α-Glucosidase

Chemoenzymatic Synthesis of trans-β-Aryl-δ-hydroxy-γ-lactones and Enzymatic Kinetic Resolution of Their Racemic Mixtures

A Simple, Efficient Synthesis of 2-Aryl Benzimidazoles Using Silica Supported Periodic Acid Catalyst and Evaluation of Anticancer Activity

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