- Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities
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The natural product lupeol 1 was isolated from aerial parts of Vernonia scorpioides with satisfactory yield, which made it viable to be used as starting material in semisynthetic approach. Ten lupeol derivatives 2–11 were prepared by classical procedures. Including, five new esters derivatives 7–11, which were obtained by structural modifications in the isopropylidene fragment. All semisynthetic compounds and lupeol 1–11 were confirmed by 1H NMR, 13C NMR and HRMS. Their antiprotozoal activity was evaluated in vitro against L. amazonensis and T. cruzi. Derivative 6 showed the best antitrypanosomal activity (IC50?=?12.48?μg/mL) and the lowest cytotoxic derivative (CC50?=?161.50?μg/mL). The mechanism of action of the most active derivatives (4, 6 and 11) is not dependent from the enzyme trypanothione reductase.
- Machado, Vanessa R.,Sandjo, Louis P.,Pinheiro, Giovanni L.,Moraes, Milene H.,Steindel, Mario,Pizzolatti, Moacir G.,Biavatti, Maique W.
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p. 275 - 281
(2017/10/06)
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- Oxidation at C-16 enhances butyrylcholinesterase inhibition in lupane triterpenoids
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A set of triterpenoids with different grades of oxidation in the lupane skeleton were prepared and evaluated as cholinesterase inhibitors. Allylic oxidation with selenium oxide and Jones's oxidation were employed to obtain mono-, di- and tri-oxolupanes, starting from calenduladiol (1) and lupeol (3). All the derivatives showed a selective inhibition of butyrylcholinesterase over acetylcholinesterase (BChE vs. AChE). A kinetic study proved that compounds 2 and 9, the more potent inhibitors of the series, act as competitive inhibitors. Molecular modeling was used to understand their interaction with BChE, the role of carbonyl at C-16 and the selectivity towards this enzyme over AChE. These results indicate that oxidation at C-16 of the lupane skeleton is a key transformation in order to improve the cholinesterase inhibition of these compounds.
- Castro, María Julia,Richmond, Victoria,Faraoni, María Belén,Murray, Ana Paula
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p. 301 - 309
(2018/05/28)
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- Synthesis of new heterocyclic lupeol derivatives as nitric oxide and pro-inflammatory cytokine inhibitors
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A series of heterocyclic derivatives including indoles, pyrazines along with oximes and esters were synthesized from lupeol and evaluated for anti-inflammatory activity through inhibition of lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW 264.7 and J774A.1 cells. All the synthesized molecules of lupeol were found to be more active in inhibiting NO production with an IC50 of 18.4-48.7 μM in both the cell lines when compared to the specific nitric oxide synthase (NOS) inhibitor, L-NAME (IC50 = 69.21 and 73.18 μM on RAW 264.7 and J774A.1 cells, respectively). The halogen substitution at phenyl ring of indole moiety leads to potent inhibition of NO production with half maximal concentration ranging from 18.4 to 41.7 μM. Furthermore, alkyl (11, 12) and p-bromo/iodo (15, 16) substituted compounds at a concentration of 20 μg/mL exhibited mild inhibition (29-42%) of LPS-induced tumor necrosis factor alpha (TNF-α) and weak inhibition (10-22%) towards interleukin 1-beta (IL-1β) production in both the cell lines. All the derivatives were found to be non-cytotoxic when tested at their IC50 (μM). These findings suggest that the derivatives of lupeol could be a lead to potent inhibitors of NO.
- Bhandari, Pamita,Patel, Neeraj Kumar,Bhutani, Kamlesh Kumar
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p. 3596 - 3599
(2014/07/22)
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- Design and synthesis of lupeol analogues and their glucose uptake stimulatory effect in L6 skeletal muscle cells
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Structure modifications of lupeol at the isopropylene moiety have been described via allylic oxidation using selenium dioxide. The antidiabetic efficacy of lupeol analogues were evaluated in vitro as glucose uptake stimulatory effect in L6 skeletal muscle cells. From all tested compounds, 2, 3, 4b and 6b showed significant stimulation of glucose uptake with respective percent stimulation of 173.1 (p 0.001), 114.1 (p 0.001), 98.3 (p 0.001) and 107.3 (p 0.001) at 10 μM concentration. Stimulation of glucose uptake by these compounds is associated with enhanced translocation of glucose transporter 4 (GLUT4) and activation of IRS-1/PI3-K/AKT-dependent signaling pathway in L6 cells. Structure-activity relationship analysis of these analogues demonstrated that the integrity of α,β-unsaturated carbonyl and acetyl moieties were important in the retention of glucose uptake stimulatory effect. It is therefore proposed that naturally occurring lupeol and their analogues might reduce blood glucose, at least in part, through stimulating glucose utilization by skeletal muscles.
- Khan, Mohammad Faheem,Maurya, Chandan Kumar,Dev, Kapil,Arha, Deepti,Rai, Amit Kumar,Tamrakar, Akhilesh Kumar,Maurya, Rakesh
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supporting information
p. 2674 - 2679
(2014/06/09)
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- Novel class of hybrid natural products derived from lupeol (Part-Iii) pharmacomodulation on lupeol skeleton: Design, synthesis and biological evaluation of novel lupeol derivatives as antimalarial agents
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Novel hybrid lupeol heterocyclics (quinoline, pyrimidine and pyrazole) were prepared. Triterpene lupeol 1 isolated from plant Crataeva nurvala was chemically modified and hybrid natural products 2a, 3a-p, 4a-p, 5a-b, 6e, 7a-b, 8a-c, 9 and 10 were evaluated for antimalarial activity in vitro. Compounds 3g, 3e, 3i, 4e, 4f, 5e, 7b and 8c showed MIC against chloroquine sensitive 3D7 strain of P. falciparum at 10 μg/ml.
- Mishra, Namita,Kumar, Satish,Khare, Pritibha,Raj, Kanwal
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- Synthesis and anti-HIV activity of lupane and olean-18-ene derivatives. Absolute configuration of 19,20-epoxylupanes by VCD
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Lupane triterpenoids 2 and 5-12 and oleanene derivatives 13 and 14 were prepared from lupeol (1), betulin (3), and germanicol (4). They were tested for anti-HIV activity, and some structure-activity relationships were outlined. The 20-(S) absolute configuration of epoxylupenone (8) was assessed by comparison of the observed and DFT-calculated vibrational circular dichroism spectra. The CompareVOA algorithm was employed to support the C-20 configuration assignment. The 20,29 double bond in lupenone (2) and 3-epilupeol (15) was stereoselectively epoxidized to produce 20-(S)-8 and 20-(S)-16, respectively, an assignment in agreement with their X-ray diffraction structures.
- Gutierrez-Nicolas, Fatima,Gordillo-Roman, Barbara,Oberti, Juan C.,Estevez-Braun, Ana,Ravelo, Angel G.,Joseph-Nathan, Pedro
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experimental part
p. 669 - 676
(2012/06/29)
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- Lichens and Fungi. XVIII. Extractives from Pseudocyphellaria rubella
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Twenty lupane triterpenoids including five (20RS)-epimeric pairs have been isolated from the chloroform extractives of the lichen Pseudocyphellaria rubella.The utility of g.c.-m.s. procedures in the structural elucidation of the extractives, some of which were complex mixtures is discussed.
- Corbett, R. Edward,Cong, Aimy N. T.,Holland, Patrick T.,Wilkins, Alistair L.
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p. 461 - 468
(2007/10/02)
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