Abstract：
:Indole alkaloids possess a large spectrum of biological activities including anti-protozoal action. Here we report for the first time that voacamine, isolated from the plant Tabernaemontana coronaria, is an antiprotozoal agent effective against a large array of trypanosomatid parasites including Indian strain of Leishmania donovani and Brazilian strains of Leishmania amazonensis and Trypanosoma cruzi. It inhibits the relaxation activity of topoisomerase IB of L. donovani (LdTop1B) and stabilizes the cleavable complex. Voacamine is probably the first LdTop1B-specific poison to act uncompetitively. It has no impact on human topoisomerase I and II up to 200μM concentrations. The study also provides a thorough insight into ultrastructural alterations induced in three kinetoplastid parasites by a specific inhibitor of LdTop1B. Voacamine is also effective against intracellular amastigotes of different drug unresponsive field isolates of Leishmania donovani obtained from endemic zones of India severely affected with visceral leishmaniasis. Most importantly, this is the first report demonstrating the efficacy of a compound to reduce the burden of drug resistant parasites, unresponsive to SAG, amphotericin B and miltefosine, in experimental BALB/c mice model of visceral leishmaniasis. The findings cumulatively provide a strong evidence that voacamine can be a promising drug candidate against trypanosomatid infections.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Chowdhury SR,Kumar A,Godinho JLP,De Macedo Silva ST,Zuma AA,Saha S,Kumari N,Rodrigues JCF,Sundar S,Dujardin JC,Roy S,De Souza W,Mukhopadhyay S,Majumder HKdoi
10.1016/j.bcp.2017.05.002subject
Has Abstractpub_date
2017-08-15 00:00:00pages
19-30eissn
0006-2952issn
1873-2968pii
S0006-2952(17)30251-4journal_volume
138pub_type
杂志文章abstract：UNLABELLED:Non-steroidal anti-inflammatory drugs (NSAIDs) induce the shedding of L-selectin in human neutrophils through a mechanism still not well understood. In this work we studied both the functional effect of NSAIDs on the neutrophils/endothelial cells dynamic interaction, and the potential involvement of reactive...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2012.10.024
更新日期：2013-01-15 00:00:00
abstract：:Cancer develops through a series of genetic changes leading to malignant transformation. Numerous gene and pathways involved in stages of progression to frank malignancy have been elucidated. These genetic changes result in aberrations in fundamental cellular processes controlling proliferation, apoptosis, differentia...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.03.004
更新日期：2006-08-28 00:00:00
abstract：:Blood samples from 140 healthy German volunteers were used to further characterize the genetic polymorphism of the human theta class glutathione S-transferase 1 (GSTT1). For measurements of GSTT1 activity, hemolysates were incubated in vitro with different concentrations of dichloromethane. The resulting enzymatically...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00191-9
更新日期：1998-11-01 00:00:00
abstract：:Four pseudo-symmetrical tamoxifen derivatives, RID-B (13), RID-C (14), RID-D (15), and bis(dimethylaminophenetole) (16), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of these pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 13 ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.11.005
更新日期：2008-03-01 00:00:00
abstract：:We report here studies on the regulation of the metabolism of adenosine 3',5'-monophosphate (cAMP) in established and primary cultures of rat pulmonary microvascular endothelial cells (RPMVEC). Inhibition by rolipram, a selective inhibitor of cAMP phosphodiesterase (PDE) of the PDE4 gene family, was required to achiev...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00914-5
更新日期：2002-02-15 00:00:00
abstract：:Multidrug resistance mediated by the multidrug resistance-associated protein MRP1 is associated with decreased drug accumulation, which is in turn dependent on cellular glutathione. We have reported that verapamil, an inhibitor of drug transport, caused a decrease in cellular glutathione in CCRF-CEM/E1000 MRP1-overexp...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00681-5
更新日期：2001-08-15 00:00:00
abstract：:The levels and subcellular distribution of enzymes involved in defenses against reactive oxygen superoxide dismutase (SOD; E.C.1.15.1.1), glutathione peroxidase (GPX; E.C.1.11.1.9), catalase (CAT; E.C.1.11.1.6), and DT-diaphorase (DT; E.C.1.6.99.2) and of the conjugating enzymes glutathione transferase (GST; E.C.2.5.1...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00185-9
更新日期：1999-10-15 00:00:00
abstract：:We have investigated the antitumor and apoptotic effects of 1, 25-dihydroxyvitamin D(3) (VD(3)) in glioma cell lines and in primary cultures derived from surgical specimens from patients. Our results showed that certain glioma cells underwent apoptosis, whereas others were resistant. In an attempt to search for parame...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00438-x
更新日期：2000-11-01 00:00:00
abstract：:Partial hepatectomy (PH) (70% resection) causes within 4 hr an accumulation of ornithine decarboxylase (EC 4.1.1.17, ODC) mRNAs concomitant with an increase in ODC activity, maximum values being observed at 8 and 16 hr, respectively. In the early hours of hepatic regeneration, enhancement of transcriptional-rate of OD...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90462-t
更新日期：1990-10-01 00:00:00
abstract：:Reactive oxygen and nitrogen species are overproduced in the cardiovascular system in response to the exposure to doxorubicin, a cardiotoxic anticancer compound. Oxidant-induced cell injury involves the activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) and pharmacological inhibition of PARP has recen...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.11.023
更新日期：2005-03-01 00:00:00
abstract：:A critical processing step in endothelin biosynthesis is the conversion of the intermediate "big endothelin" to its biologically active product catalysed by endothelin converting enzyme (ECE). In this commentary we discuss critically the cellular location, structure, and activity of the isoforms of ECE. The current ev...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/0006-2952(95)02036-5
更新日期：1996-01-26 00:00:00
abstract：:Characteristics of erythromycin binding to Staphylococcus aureus were determined by using kinetics and equilibrium binding experiments. Both methods yielded identical values of the dissociation constant, i.e. 0.1 muM. This value was in accord with that found with a bacterial extract of ribosomes which are the organell...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90090-0
更新日期：1986-03-15 00:00:00
abstract：:Multiple sclerosis (MS) is a severe chronic T cell-mediated autoimmune inflammatory disease of the central nervous system (CNS), the existing therapy of which is only partially effective and is associated with undesirable side effects. Euphol, an alcohol tetracyclic triterpene, has a wide range of pharmacological prop...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.11.026
更新日期：2012-02-15 00:00:00
abstract：:Cyclophosphamides are pro-drugs whose killing agent is produced from an aldehyde that is formed by the action of a P450 oxidation step. The mustard from the aldehyde can destroy bone marrow cells as well as the tumor. Aldehyde dehydrogenase (EC 1.2.1.3) can oxidize the aldehyde and hence inactivate the cytotoxic inter...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2008.06.018
更新日期：2008-09-01 00:00:00
abstract：:The effect of the adenosine deaminase (ADA) inhibitor 2'-deoxycoformycin (dCF) on the development of insulin-dependent diabetes mellitus (IDDM) was assessed in the BB Wistar rat. Sixty-one male rats were treated from days 30 to 120 with 0, 0.5, 1.0 or 1.5 mg dCF/kg/week. The incidence of IDDM was 78% in the controls a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(93)90672-j
更新日期：1993-09-14 00:00:00
abstract：:CCl4 induced cellular injury and its modification by prostacyclin (PGI2) was studied in cultured rat hepatocytes. Biosynthesis of both intracellular and serum proteins and that of phospholipids decreased upon CCl4 treatments (IC50 7.0, 2.5 and 3.2 mM, respectively). After 1 hr exposure of the cells to CCl4, the reduct...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90443-o
更新日期：1990-10-01 00:00:00
abstract：:Polycyclic aromatic hydrocarbon (PAH)-type compounds induce at least two rat UDP-glucuronosyltransferase isoforms, UGT1A6 and UGT1A7. Among the glucuronidation reactions of PAH metabolites studied, mono- and diglucuronide formation of benzo[a]pyrene and chrysene-3,6-diphenol showed the highest induction factors in rat...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00337-2
更新日期：1999-03-15 00:00:00
abstract：:HO-1 (heme oxygenase-1), an antioxidant enzyme, induced by rosiglitazone (PPAR ligands) can be a potential treatment of inflammation. However, the mechanisms of rosiglitazone-induced HO-1 expression in human pulmonary alveolar epithelial cells (HPAEpiCs) remain largely unknown. In this study, we found that upregulatio...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2017.12.024
更新日期：2018-02-01 00:00:00
abstract：:Local anaesthetics and opioid drugs function synergistically to provide analgesia. In the present study, the nature of this synergy has been investigated using in vitro radioligand binding to determine whether the local anaesthetics bupivacaine and tetracaine modulate the binding of two kappa-opioid receptor ligands, ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(94)00512-k
更新日期：1995-03-30 00:00:00
abstract：:The relationship between DNA crosslinks and cell death as a result of exposure to melphalan (MLN) was studied in the F1 variant of B16 melanoma cells. The formation of DNA crosslinks is believed to represent the lethal lesion following exposure of cells to bifunctional alkylating agents. The production of DNA crosslin...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(88)90319-x
更新日期：1988-08-15 00:00:00
abstract：:In this study we investigated whether NADH fluorescence levels changed in response to low or high rates of electrical stimulation in single ventricular myocytes isolated from rat and guinea-pig hearts, either during a single contraction or upon sustained electrical stimulation of cells. NADH levels were determined fro...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(98)00016-1
更新日期：1998-07-15 00:00:00
abstract：:Dicumarol is routinely added to the 3-[4,4-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay to study the role of NAD(P)H:quinone oxido-reductase in drug activation and detoxification. We assessed the direct impact of dicumarol (a mitochondrial uncoupler) on the MTT assay. Mouse mammary tumor (EMT6) an...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00240-5
更新日期：2003-07-15 00:00:00
abstract：:In the present study, a novel synthetic compound 4-(2-(cyclohex-2-enylidene)hydrazinyl)quinolin-2(1H)-one (CYL-4d) was found to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) production without affecting cell viability or enzyme activity of expressed inducible NO synthase (iNOS) in RAW 264.7 macrophages. C...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.02.009
更新日期：2007-06-01 00:00:00
abstract：:Pancreatic cancer is a major cause of cancer-related mortality around the world. Currently, options for diagnosis and treatment are extremely limited, which culminates in a very high mortality rate. Intensive research spanning more than four decades has met several roadblocks in terms of improvement in overall surviva...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2019.05.025
更新日期：2019-08-01 00:00:00
abstract：:Poly (ADP-ribose) polymerases (PARPs) facilitate repairing of cancer cell DNA damage as a mean to promote cancer proliferation and metastasis. Inhibitors of PARPs which interfering DNA repair, in context of defects in other DNA repair mechanisms, can thus be potentially exploited to inhibit or even kill cancer cells. ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2016.02.015
更新日期：2016-05-01 00:00:00
abstract：:Continuous in vitro cultivation of human lymphoid H9 cells in the presence of 0.5microM arabinosyl-cytosine (araC) resulted in cell variant, H9-araC cells, that was >600-fold resistant to the drug and cross resistant to its analogs and other unrelated nucleosides, e.g. dideoxycytidine (5-fold), thiacytidine (2-fold), ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2005.05.014
更新日期：2005-08-01 00:00:00
abstract：:A2B adenosine receptor (A2BAR) activation induces Gs-dependent cyclic AMP accumulation. However, A2BAR G protein-coupling to other signaling events, e.g. ERK1/2 and calcium, is not well documented. We explored Gi, Gq/11 and Gs coupling in 1321 N1 astrocytoma, HEK293, and T24 bladder cancer cells endogenously expressin...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2017.12.003
更新日期：2018-05-01 00:00:00
abstract：:B-Raf kinase is the key point in a main branch of mitogen-activated protein kinase pathways and some of its mutations, such as the V600E mutation, lead to the persistent activation of ERK signaling and the trigger of severe diseases, including melanoma and other somatic cancers. Several potent drugs have been approved...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2017.02.022
更新日期：2017-05-15 00:00:00
abstract：:The ex vivo sensitivity of murine pluripotent hematopoietic stem cells (CFU-S) and myeloid progenitor cells (CFU-GM) to 4-hydroperoxycyclophosphamide, ASTA Z 7557, phosphoramide mustard, acrolein, melphalan, and cis-platinum was determined in the absence and presence of known (disulfiram, diethyldithiocarbamate, cyana...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90719-1
更新日期：1985-10-01 00:00:00
abstract：:Ectonucleotidases are key for purinergic signaling. They control the duration of activity of purinergic receptor agonists. At the same time, they produce hydrolysis products as additional ligands of purinergic receptors. Due to the considerable diversity of enzymes, purinergic receptor ligands and purinergic receptors...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2020.114322
更新日期：2020-11-06 00:00:00
