Displaying publications 1 - 20 of 35 in total

Abstract:
Sort:
  1. Anti-Amyloid β Aggregation Activity and Cell Viability Effect of Betacyanins from Red Pitahaya (Hylocereus polyrhizus) for Alzheimer's Disease
    Thwe PN, Yeong KY, Choo WS
    Plant Foods Hum Nutr, 2023 Sep;78(3):613-619.
    PMID: 37466824 DOI: 10.1007/s11130-023-01081-7
    Betacyanin-rich extract from red beet (Beta vulgaris) was recently reported to inhibit amyloid β (Aβ) aggregation, a main pathological event in Alzheimer's disease. However, the anti-Aβ aggregation effect of individual betacyanin isolates has not been reported before. This study investigated the anti-Aβ aggregation activity and cytotoxicity of betacyanins from red pitahaya or red dragon fruit (Hylocereus polyrhizus). Betacyanin fraction (IC50 = 16.02 ± 1.15 µg/mL) and individual betacyanin isolates exhibited anti-Aβ aggregation activity in a concentration-dependent manner using a thioflavin T fluorescence assay. The highest to lowest IC50 was in the order of betanin (426.30 ± 29.55 µM), phyllocactin (175.22 ± 1.52 µM), and hylocerenin (131.73 ± 5.58 µM), following a trend of increase in functional groups of carboxyl, hydroxyl, and/or carbonyl. Further, the betacyanin fraction of 135.78 µg/mL and below, which were concentrations with an anti-Aβ aggregation effect, were validated as non-neurotoxic based on an in vitro cytotoxicity assay using human neuroblastoma (SH-SY5Y) cells. These findings highlight the potential neuroprotective activity of betacyanins for Alzheimer's disease.
    Matched MeSH terms: Neuroblastoma*
  2. Neuroblastoma and diagnostic imaging
    Sherazi ZA, Abdullah AW, Malik AS, Saad R
    Ann Acad Med Singap, 1993 Sep;22(5):701-6.
    PMID: 8267349
    To assess the utility of the current imaging modalities, a six-year retrospective study was conducted from May 1985 through April 1991 on 11 patients with histopathologically confirmed neuroblastoma. There were four males and seven females. Median age at presentation was six years. All patients underwent intravenous urography (IVU), abdominal ultrasonography (US), skeletal surveys and bone marrow aspiration. Computed tomographic (CT) scanning was performed in nine patients and trephine bone biopsy in five. Suprarenal gland was the primary site in six patients, including one bilateral neuroblastoma. Two presented with primary paraspinal mass, one with posterior mediastinal mass, one had a retroperitoneal tumour and one presented as primary cerebral neuroblastoma. IVU showed indirect evidence of suprarenal tumours in five patients. US demonstrated suprarenal mass in six and calcification within the mass in five patients. US also documented retroperitoneal lymphadenopathy in five patients. US-guided fine needle aspiration biopsy was performed in seven patients and it gave correct histological diagnosis in all. CT accurately depicted all the primary tumours and their involvement of the surrounding structures and metastases in the brain and orbits. US proved to be quite accurate in diagnosing primary abdominal tumours despite its limitations but in other sites, CT was of greater help. Solid appearance of a suprarenal mass on US made the diagnosis of neuroblastoma very likely and calcification within the mass further supported the diagnosis.
    Matched MeSH terms: Neuroblastoma/diagnosis*
  3. a case with massive metastases to bone and soft tissues of arm
    Lopez CG, Ganesan S, Dutt AK, Omar bin Din
    Med J Malaya, 1969 Dec;24(2):154-7.
    PMID: 4244143
    Matched MeSH terms: Neuroblastoma*
  4. Neuroblastoma in Malaysian children
    Sinniah D, Choo M, Somasundram K
    Med J Malaysia, 1979 Dec;34(2):149-53.
    PMID: 548717
    Matched MeSH terms: Neuroblastoma/pathology*
  5. Fulltext Stage IV-S neuroblastoma. A review from the University Hospital , Kuala Lumpur
    Sinniah D, Lin HP, Kwan PW, Somasundram K
    PMID: 7344086
    A review of 20 cases of neuroblastoma at the University Hospital, Kuala Lumpur from 1967 to 1980 reveals six infants aged 2 to 13 months with stage IV·S disease, associated with an unusually good prognosis. Four of the six patients presented with hepatomegaly, one had skin nodules and another paresis of the lower limbs. The primary tumour was located infra-diaphragmatically in all cases, four had disease in the bone marrow but none had radiological evidence of bone involvement. Although not systematic, with limited treatment of low dose radiation and mild chemotherapy, four patients are alive and well, one absconded and one died of septicaemia. It is important to define this special category as an unexpectedly good survival is possible with minimal therapy. Death is more likely to result from over-zealous treatment than from the disease itself.
    Matched MeSH terms: Neuroblastoma*
  6. CD44s expression correlated with the International Neuroblastoma Pathology Classification (Shimada system) for neuroblastic tumours
    Munchar MJ, Sharifah NA, Jamal R, Looi LM
    Pathology, 2003 Apr;35(2):125-9.
    PMID: 12745459
    CD44 is a cell adhesion molecule that plays an important role in the cascade of metastasis and progression of human malignant tumours. A large family of variants or isoforms, generated by alternative splicing of a single gene, has been reported to be involved in the malignant process by conferring metastatic potential to non-metastatic cells. The objective of this study was to compare the expression of CD44 standard molecule with the International Neuroblastoma Pathology Classification (INPC) for neuroblastic tumours, a histological grading system based on the Shimada system for predicting the clinical outcome in neuroblastic tumours.
    Matched MeSH terms: Neuroblastoma/classification; Neuroblastoma/metabolism*; Neuroblastoma/pathology
  7. Fulltext Intracranial metastatic neuroblastoma mimicking subdural empyema: an interesting case
    Hairuddin NF, Musa AT, Abdullah MS
    Malaysian Journal of Paediatrics and Child Health, 2016;22(1):66-70.
    MyJurnal
    Neuroblastoma is usually presented with abdominal distension. However, central nervous system manifestations of neuroblastoma are uncommon. In this case report, patient presented with uncommon presentation of neuroblastoma and the diagnostic dilemma.
    Matched MeSH terms: Neuroblastoma
  8. Fulltext Preliminary report on somatostatin receptor imaging in rare endocrine tumours
    Abdullah BJJ, Paramsothy M, Khir ASM, Chan SP
    Med J Malaysia, 2000 Jun;55(2):169-73.
    PMID: 19839144
    Our preliminary experience of Somatostatin Receptor Positive Tumour Scintigraphy (SRPTS) in the management of some rare neuroendocrine tumours is highlighted. Six patients were evaluated using SRPTS. A single patient each with Zollinger-Ellison syndrome, recurrent medullary carcinoma of thyroid and Stage IV neuroblastoma. Two patients with phaeochromocytoma, and one patient with suspected insulinoma were evaluated. SRPTS was useful in three of the six patients studied i.e. patient with gastrinoma, recurrent medullary carcinoma of thyroid and metastatic neuroblastoma. SRPTS although expensive is a useful and cost-effective approach of rare endocrine tumours and it role as a first line tool in the diagnosis is discussed.
    Matched MeSH terms: Neuroblastoma/diagnosis; Neuroblastoma/physiopathology; Neuroblastoma/radionuclide imaging*; Neuroblastoma/ultrasonography
  9. Natural Terpenes Inhibit the Cytopathogenicity of Naegleria fowleri Causing Primary Amoebic Meningoencephalitis in the Human Cell Line Model
    Rajendran K, Ahmed U, Meunier AC, Shaikh MF, Siddiqui R, Anwar A
    ACS Chem Neurosci, 2023 Dec 06;14(23):4105-4114.
    PMID: 37983556 DOI: 10.1021/acschemneuro.3c00258
    Naegleria fowleri is one of the free-living amoebae and is a causative agent of a lethal and rare central nervous system infection called primary amoebic meningoencephalitis. Despite the advancement in antimicrobial chemotherapy, the fatality rate in the reported cases is more than 95%. Most of the treatment drugs used against N. fowleri infection are repurposed drugs. Therefore, a large number of compounds have been tested against N. fowleri in vitro, but most of the compounds showed high toxicity. To overcome this, we evaluated the effectiveness of naturally occurring terpene compounds against N. fowleri. In this study, we evaluated the antiamoebic potential of natural compounds including Thymol, Borneol, Andrographolide, and Forskolin againstN. fowleri. Thymol showed the highest amoebicidal activity with IC50/24 h at 153.601 ± 19.6 μM. Two combinations of compounds Forskolin + Thymol and Forskolin + Borneol showed a higher effect on the viability of trophozoites as compared to compounds alone and hence showed a synergistic effect. The IC50 reported for Forskolin + Thymol was 81.30 ± 6.86 μM. Borneol showed maximum cysticidal activity with IC50/24 h at 192.605 ± 3.01 μM. Importantly, lactate dehydrogenase release testing revealed that all compounds displayed minimal cytotoxicity to human HaCaT, HeLa, and SH-SY5Y cell lines. The cytopathogenicity assay showed that Thymol and Borneol also significantly reduced the host cell cytotoxicity of pretreated amoeba toward the human HaCaT cell line. So, these terpene compounds hold potential as therapeutic agents against infections caused by N. fowleri and are potentially a step forward in drug development against this deadly pathogen as these compounds have also been reported to cross the blood-brain barrier. Therefore, an in vivo study using animal models is necessary to assess the efficacy of these compounds and the need for further research into the intranasal route of delivery for the treatment of these life-threatening infections.
    Matched MeSH terms: Neuroblastoma*
  10. PPARβ/δ-ANGPTL4 axis mediates the promotion of mono-2-ethylhexyl phthalic acid on MYCN-amplified neuroblastoma development
    Liu Y, Hamid N, Manzoor R, Zhang BF, Liao YL, Wang JX, et al.
    Sci Total Environ, 2024 Feb 20;912:168949.
    PMID: 38042186 DOI: 10.1016/j.scitotenv.2023.168949
    Di-2-ethylhexyl phthalic acid (DEHP) is one of the most widely used plasticizers in the industry, which can improve the flexibility and durability of plastics. It is prone to migrate from various daily plastic products through wear and leaching into the surrounding environment and decompose into the more toxic metabolite mono-2-ethylhexyl phthalic acid (MEHP) after entering the human body. However, the impacts and mechanisms of MEHP on neuroblastoma are unclear. We exposed MYCN-amplified neuroblastoma SK-N-BE(2)C cells to an environmentally related concentration of MEHP and found that MEHP increased the proliferation and migration ability of tumor cells. The peroxisome proliferator-activated receptor (PPAR) β/δ pathway was identified as a pivotal signaling pathway in neuroblastoma, mediating the effects of MEHP through transcriptional sequencing analysis. Because MEHP can bind to the PPARβ/δ protein and initiate the expression of the downstream gene angiopoietin-like 4 (ANGPTL4), the PPARβ/δ-specific agonist GW501516 and antagonist GSK3787, the recombinant human ANGPTL4 protein, and the knockdown of gene expression confirmed the regulation of the PPARβ/δ-ANGPTL4 axis on the malignant phenotype of neuroblastoma. Based on the critical role of PPARβ/δ and ANGPTL4 in the metabolic process, a non-targeted metabolomics analysis revealed that MEHP altered multiple metabolic pathways, particularly lipid metabolites involving fatty acyls, glycerophospholipids, and sterol lipids, which may also be potential factors promoting tumor progression. We have demonstrated for the first time that MEHP can target binding to PPARβ/δ and affect the progression of neuroblastoma by activating the PPARβ/δ-ANGPTL4 axis. This mechanism confirms the health risks of plasticizers as tumor promoters and provides new data support for targeted prevention and treatment of neuroblastoma.
    Matched MeSH terms: Neuroblastoma*
  11. Genes associated with amyloid-beta-induced inflammasome-mediated neuronal death identified using functional gene trap mutagenesis approach
    Yap JKY, Pickard BS, Gan SY, Chan EWL
    Int J Biochem Cell Biol, 2021 07;136:106014.
    PMID: 34022435 DOI: 10.1016/j.biocel.2021.106014
    Alzheimer's disease is an irreversible neurodegenerative disease, which accounts for most dementia cases. Neuroinflammation is increasingly recognised for its roles in Alzheimer's disease pathogenesis which, in part, links amyloid-beta to neuronal death. Neuroinflammatory signalling can be exhibited by neurons themselves, potentially leading to widespread neuronal cell death, although neuroinflammation is commonly associated with glial cells. The presence of the inflammasomes such as nucleotide-binding leucine-rich repeat receptors protein 1 in neurons accelerates amyloid-beta -induced neuroinflammation and has been shown to trigger neuronal pyroptosis in murine Alzheimer's disease models. However, the pathways involved in amyloid-beta activation of inflammasomes have yet to be elucidated. In this study, a gene trap mutagenesis approach was utilised to resolve the genes functionally involved in inflammasome signalling within neurons, and the mechanism behind amyloid-beta-induced neuronal death. The results indicate that amyloid-beta significantly accelerated neuroinflammatory cell death in the presence of a primed inflammasome (the NLR family pyrin domain-containing 1). The mutagenesis screen discovered the atypical mitochondrial Ras homolog family member T1 as a significant contributor to amyloid-beta-induced inflammasome -mediated neuronal death. The mutagenesis screen also identified two genes involved in transforming growth factor beta signalling, namely Transforming Growth Factor Beta Receptor 1 and SNW domain containing 1. Additionally, a gene associated with cytoskeletal reorganisation, SLIT-ROBO Rho GTPase Activating Protein 3 was found to be neuroprotective. In conclusion, these genes could play important roles in inflammasome signalling in neurons, which makes them promising therapeutic targets for future drug development against neuroinflammation in Alzheimer's disease.
    Matched MeSH terms: Neuroblastoma/etiology; Neuroblastoma/metabolism; Neuroblastoma/pathology*
  12. Cystic neuroblastoma with colonic fistula
    Thajunnisa bte Hassan Mohd, Yip CH
    Pediatr Radiol, 1988;18(5):406.
    PMID: 3050845
    Neuroblastoma is the most common malignant tumour in infancy originating in about 70% of cases in the adrenal gland. Haemorrhage and necrosis is often seen in neuroblastoma but cyst formation is uncommon. Fistulous communication between an adrenal cystic neuroblastoma and the large bowel has never to our knowledge been reported before.
    Matched MeSH terms: Neuroblastoma/complications*; Neuroblastoma/diagnosis
  13. p53, stem cell biology and childhood blastomas
    Oh L, Hafsi H, Hainaut P, Ariffin H
    Curr Opin Oncol, 2019 03;31(2):84-91.
    PMID: 30585860 DOI: 10.1097/CCO.0000000000000504
    PURPOSE OF REVIEW: Childhood blastomas, unlike adult cancers, originate from developing organs in which molecular and cellular features exhibit differentiation arrest and embryonic characteristics. Conventional cancer therapies, which rely on the generalized cytotoxic effect on rapidly dividing cells, may damage delicate organs in young children, leading to multiple late effects. Deep understanding of the biology of embryonal cancers is crucial in reshaping the cancer treatment paradigm for children.

    RECENT FINDINGS: p53 plays a major physiological role in embryonic development, by controlling cell proliferation, differentiation and responses to cellular stress. Tumor suppressor function of p53 is commonly lost in adult cancers through genetic alterations. However, both somatic and germline p53 mutations are rare in childhood blastomas, suggesting that in these cancers, p53 may be inactivated through other mechanisms than mutation. In this review, we summarize current knowledge about p53 pathway inactivation in childhood blastomas (specifically neuroblastoma, retinoblastoma and Wilms' tumor) through various upstream mechanisms. Laboratory evidence and clinical trials of targeted therapies specific to exploiting p53 upstream regulators are discussed.

    SUMMARY: Despite the low rate of inherent TP53 mutations, p53 pathway inactivation is a common denominator in childhood blastomas. Exploiting p53 and its regulators is likely to translate into more effective targeted therapies with minimal late effects for children. (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/COON/A23).

    Matched MeSH terms: Neuroblastoma/metabolism*; Neuroblastoma/pathology
  14. Autologous stem cell transplantation following high-dose chemotherapy in children with high-risk neuroblastoma: Practicality in resource-limited countries
    Lau SCD, Unni MNM, Teh KH, Aziz MA, Muda Z, Thomas SA, et al.
    Pediatr Blood Cancer, 2020 05;67(5):e28176.
    PMID: 31965709 DOI: 10.1002/pbc.28176
    Matched MeSH terms: Neuroblastoma/mortality*; Neuroblastoma/therapy*
  15. Fulltext Neuroprotective Effects of 7-Geranyloxycinnamic Acid from Melicope lunu ankenda Leaves
    Abdulwanis Mohamed Z, Mohamed Eliaser E, Jaafaru MS, Nordin N, Ioannides C, Abdull Razis AF
    Molecules, 2020 Aug 15;25(16).
    PMID: 32824120 DOI: 10.3390/molecules25163724
    Neurodegenerative diseases (NDDs) are chronic conditions that have drawn robust interest from the scientific community. Phytotherapeutic agents are becoming an important source of chemicals for the treatment and management of NDDs. Various secondary metabolites have been isolated from Melicope lunu-ankenda plant leaves, including phenolic acid derivatives. However, their neuroprotective activity remains unclear. Thus, the aim of this study is to elucidate the in vitro neuroprotective activity of 7-geranyloxycinnamic acid isolated from Melicope lunu-ankenda leaves. The neuroprotective activity was evaluated in differentiated human neuroblastoma (SH-SY5Y) cells by monitoring cell viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Moreover, the potential to impair apoptosis in differentiated cells was investigated employing the Annexin V-FITC assay, acridine orange and propidium iodide (AO/PI) staining, and fluorescence microscopy. Morphological assessment and ultrastructural analysis were performed using scanning and transmission electron microscopy to evaluate the effect of 7-geranyloxycinnamic acid on surface morphology and internal features of the differentiated cells. Pre-treatment of neuronal cells with 7-geranyloxycinnamic acid significantly protected the differentiated SH-SY5Y cells against H2O2-induced apoptosis. Cytoskeleton and cytoplasmic inclusion were similarly protected by the 7-geranyloxycinnamic acid treatment. The present findings demonstrate the neuroprotective potential of 7-geranyloxycinnamic acid against H2O2-induced neurotoxicity in neuronal cells, which is an established hallmark of neuronal disorders.
    Matched MeSH terms: Neuroblastoma/drug therapy*; Neuroblastoma/pathology
  16. Fulltext Presenting features and treatment outcome of 78 Malaysian children with neuroblastoma
    Ng SM, Abdullah WA, Lin HP, Chan LL
    Southeast Asian J Trop Med Public Health, 1999 Mar;30(1):149-53.
    PMID: 10695803
    To study the distribution of presenting features and their prognostic significance in neuroblastoma treated in a single institution in Malaysia. A retrospective study was made of 78 neuroblastoma cases diagnosed and treated in the University Hospital, Kuala Lumpur, Malaysia between June 1982 and February 1997. Diagnosis was established by standard histological criteria. The presenting features were evaluated for their distribution and prognostic influence. Disease-free survival from diagnosis was the outcome variable of interest. The ages ranged from 0.1 to 11 years old (median: 3 years old). The tumor originated from the adrenal glands in 83% and the majority of cases presented in advanced stage (stage III 22%, stage IV 66%). Bone marrow was the commonest site of distant metastasis occurring in 45% of patients. The main presenting signs and symptoms in decreasing order were pallor, fever, abdominal mass, weight loss, and bone/joint pain. Univariate analysis conferred age, initial stage and Hb level as significant prognostic factors. No influence in disease-free survival was found for sex, race, primary site, urinary vanillylmandelic acid level, white cell count and platelet count. Overall 2-year disease-free survival was achieved in 27 (39%) patients. Four patients underwent bone marrow transplant, three of whom achieved 2-year disease-free survival. The results suggest that age, initial stage and hemoglobin level are significant prognostic factors based on univariate analysis. In addition, more Malaysian children presented with adrenal primary site and advanced disease compared to previous reported studies.
    Matched MeSH terms: Neuroblastoma/complications; Neuroblastoma/diagnosis*; Neuroblastoma/mortality; Neuroblastoma/pathology; Neuroblastoma/therapy*
  17. Fulltext Ethyl acetate extract of germinated brown rice attenuates hydrogen peroxide-induced oxidative stress in human SH-SY5Y neuroblastoma cells: role of anti-apoptotic, pro-survival and antioxidant genes
    Azmi NH, Ismail N, Imam MU, Ismail M
    BMC Complement Altern Med, 2013;13:177.
    PMID: 23866310 DOI: 10.1186/1472-6882-13-177
    There are reports of improved metabolic outcomes due to consumption of germinated brown rice (GBR). Many of the functional effects of GBR can be linked to its high amounts of antioxidants. Interestingly, dietary components with high antioxidants have shown promise in the prevention of neurodegenerative diseases like Alzheimer's disease (AD). This effect of dietary components is mostly based on their ability to prevent apoptosis, which is believed to link oxidative damage to pathological changes in AD. In view of the rich antioxidant content of GBR, we studied its potential to modulate processes leading up to AD.
    Matched MeSH terms: Neuroblastoma/genetics; Neuroblastoma/metabolism*; Neuroblastoma/physiopathology
  18. Fulltext The antimalarial drug quinine interferes with serotonin biosynthesis and action
    Islahudin F, Tindall SM, Mellor IR, Swift K, Christensen HE, Fone KC, et al.
    Sci Rep, 2014 Jan 09;4:3618.
    PMID: 24402577 DOI: 10.1038/srep03618
    The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmitter serotonin (5-HT), here we test the hypothesis that quinine disrupts serotonin function. Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells. One possible cause of this effect is through inhibition of 5-HT receptor activation by quinine, as we observed here. Furthermore, cells exhibited marked decreases in serotonin production during incubation with quinine. By assaying activity and kinetics of the rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase (TPH2), we showed that quinine competitively inhibits TPH2 in the presence of the substrate tryptophan. The study shows that quinine disrupts both serotonin biosynthesis and function, giving important new insight to the action of quinine on mammalian cells.
    Matched MeSH terms: Neuroblastoma/pathology
  19. Fulltext Neuroprotective effects of germinated brown rice against hydrogen peroxide induced cell death in human SH-SY5Y cells
    Ismail N, Ismail M, Fathy SF, Musa SN, Imam MU, Foo JB, et al.
    Int J Mol Sci, 2012;13(8):9692-708.
    PMID: 22949825 DOI: 10.3390/ijms13089692
    The neuroprotective and antioxidative effects of germinated brown rice (GBR), brown rice (BR) and commercially available γ-aminobutyric acid (GABA) against cell death induced by hydrogen peroxide (H(2)O(2)) in human neuroblastoma SH-SY5Y cells have been investigated. Results show that GBR suppressed H(2)O(2)-mediated cytotoxicity and induced G0/G1 phase cell cycle arrest in SH-SY5Y cells. Moreover, GBR reduced mitochondrial membrane potential (MMP) and prevented phosphatidylserine (PS) translocation in SH-SY5Y cells, key features of apoptosis, and subsequent cell death. GBR exhibited better neuroprotective and antioxidative activities as compared to BR and GABA. These results indicate that GBR possesses high antioxidative activities and suppressed cell death in SH-SY5Y cells by blocking the cell cycle re-entry and apoptotic mechanisms. Therefore, GBR could be developed as a value added functional food to prevent neurodegenerative diseases caused by oxidative stress and apoptosis.
    Matched MeSH terms: Neuroblastoma/drug therapy*; Neuroblastoma/pathology*
  20. Probing simple structural modification of α-mangostin on its cholinesterase inhibition and cytotoxicity
    Khaw KY, Kumar P, Yusof SR, Ramanathan S, Murugaiyah V
    Arch Pharm (Weinheim), 2020 Nov;353(11):e2000156.
    PMID: 32716578 DOI: 10.1002/ardp.202000156
    α-Mangostin has been reported to possess a broad range of pharmacological effects including potent cholinesterase inhibition, but the development of α-mangostin as a potential lead compound is impeded by its toxicity. The present study investigated the impact of simple structural modification of α-mangostin on its cholinesterase inhibitory activities and toxicity toward neuroblastoma and liver cancer cells. The dialkylated derivatives retained good acetylcholinesterase (AChE) inhibitory activities with IC50 values between 4.15 and 6.73 µM, but not butyrylcholinesterase (BChE) inhibitory activities, compared with α-mangostin, a dual inhibitor (IC50 : AChE, 2.48 µM; BChE, 5.87 µM). Dialkylation of α-mangostin produced AChE selective inhibitors that formed hydrophobic interactions at the active site of AChE. Interestingly, all four dialkylated derivatives of α-mangostin showed much lower cytotoxicity, being 6.4- to 9.0-fold and 3.8- to 5.5-fold less toxic than their parent compound on neuroblastoma and liver cancer cells, respectively. Likewise, their selectivity index was higher by 1.9- to 4.4-fold; in particular, A2 and A4 showed improved selectivity index compared with α-mangostin. Taken together, modification of the hydroxyl groups of α-mangostin at positions C-3 and C-6 greatly influenced its BChE inhibitory and cytotoxic but not its AChE inhibitory activities. These dialkylated derivatives are viable candidates for further structural modification and refinement, worthy in the search of new AChE inhibitors with higher safety margins.
    Matched MeSH terms: Neuroblastoma/drug therapy*; Neuroblastoma/pathology
Related Terms
Filters
Contact Us

Please provide feedback to Administrator ([email protected])

External Links