Denver T Hendricks

University of Cape Town, Kaapstad, Western Cape, South Africa

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Publications (46)184.58 Total impact

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    ABSTRACT: A series of mono- and bis-salicylaldimine ligands and their corresponding Rh(i) complexes were prepared. The compounds were characterised using standard spectroscopic techniques including NMR, IR spectroscopy and mass spectrometry. The salicylaldimine ligands and complexes were screened for antiparasitic activity against two strains of Plasmodium falciparum i.e. the NF54 CQ-sensitive and K1 CQ-resistant strain as well as against the G3 isolate of Trichomonas vaginalis. The monomeric salicylaldimine quinolines exhibited good activity against the NF54 strain and the dimeric salicylaldimine quinolines exhibited no cross resistance across the two strains. The binuclear 5-chloro Rh(i) complex displayed the best activity against the Trichomonas vaginalis parasite, possibly a consequence of its enhanced lipophilicity. The compounds were also screened for cytotoxicity in vitro against WHCO1 oesophageal cancer cells. The monomeric salicylaldimine quinolines exhibited high selectivity towards malaria parasites compared to cancer cells, while the dimeric compounds were less selective.
    No preview · Article · Jul 2015 · Dalton Transactions
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    ABSTRACT: Ferrocenyl azines containing salicylaldimine motifs were prepared by Schiff-base condensation of salicylaldehyde hydrazones and (dimethylamino)methyl ferrocenecarboxaldehyde. Their corresponding Rh(I) complexes were prepared by reaction of the various ferrocenyl azines with [RhCl(COD)]2 (where COD = 1,5-cyclooctadiene) to yield heterobimetallic complexes. The compounds were characterized using standard spectroscopic and analytical techniques. The characterization data suggests that the ferrocenyl azine acts as a bidentate donor. The rhodium(I) centre binds to the imine nitrogen and phenolic oxygen of the salicylaldimine, forming a neutral complex. The compounds were screened against the NF54 chloroquine-sensitive (CQS) and K1 chloroquine-resistant (CQR) strains of Plasmodium falciparum. The ferrocene-containing salicylaldimines exhibited weak to moderate activity across both parasite strains. The heterometallic complexes exhibited enhanced activity compared to the ferrocenyl azines in both strains. Most of the compounds exhibited enhanced activity in the resistant strain compared to the sensitive strain. Inhibition of haemozoin formation was considered as a possible mechanism of action of these compounds and indeed they exhibited β-haematin inhibition activity, albeit weaker than chloroquine. All compounds were also screened against the G3 strain of Trichomonas vaginalis. The compounds inhibited no more than 50% parasite growth at the tested concentration. One complex exhibited moderate cytotoxicity against WHCO1 oesophageal cancer cells.
    No preview · Article · Jul 2015 · Journal of Organometallic Chemistry
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    Katie E Hadley · Denver T Hendricks

    Full-text · Dataset · Jun 2014
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    ABSTRACT: The nuclear export receptor, Crm1 (exportin 1), is involved in the nuclear translocation of proteins and certain RNAs from the nucleus to the cytoplasm and is thus crucial for the correct localisation of cellular components. Crm1 has recently been reported to be highly expressed in certain types of cancers, yet its expression in oesophageal cancer has not been investigated to date. We investigated the expression of Crm1 in normal and tumour tissues derived from 56 patients with human oesophageal squamous cell carcinoma and its functional significance in oesophageal cancer cell line models. Immunohistochemistry revealed that Crm1 expression was significantly elevated in oesophageal tumour tissues compared to normal tissues and its localisation shifted from predominantly nuclear to nuclear and cytoplasmic. Real‑time RT‑PCR revealed that Crm1 expression was elevated at the mRNA level. To determine the functional significance of elevated Crm1 expression in oesophageal cancer, its expression was inhibited using siRNA, and a significant decrease in cell proliferation was observed associated with G1 cell cycle arrest and the induction of apoptosis. Similarly, leptomycin B (LMB) treatment resulted in the effective killing of oesophageal cancer cells at nanomolar concentrations. Normal oesophageal epithelial cells, however, were much less sensitive to Crm1 inhibition with siRNA and LMB. Together, this study reveals that Crm1 expression is increased in oesophageal cancer and is required for the proliferation and survival of oesophageal cancer cells.
    Preview · Article · Jun 2014 · Oncology Reports
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    Katie E Hadley · Denver T Hendricks
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    ABSTRACT: Background Oesophageal squamous cell carcinoma (OSCC) is a major health burden in Sub-Saharan Africa, and novel chemotherapies are urgently required to combat this disease. The heat shock protein 90 (HSP90) inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) has previously been proposed as a possible candidate drug. NADPH quinone oxidoreductase 1 (NQO1) is known to increase the potency of 17-AAG, therefore we investigated the effects of 17-AAG in OSCC cell lines in the context of their NQO1 status. Methods We used MTT assays to compare the sensitivity of a panel of OSCC cell lines to 17-AAG. Western blotting, and RT-PCR were used to investigate NQO1 protein and mRNA levels, while an RFLP approach was used to investigate the NQO1 C609T SNP. Results Expression of NQO1 markedly increased sensitivity to 17-AAG in the OSCC cell lines, while normal fibroblasts, which expressed HSP90 at much lower levels, were more resistant to 17-AAG. In isolation, neither the C609T SNP, nor NQO1 mRNA levels was an accurate predictor of NQO1 protein levels. Conclusions Since NQO1 greatly enhances the anti-cancer effects of 17-AAG, this could be used as a selective marker for patients that would benefit most from 17-AAG chemotherapy at low doses. Testing for the presence of the C609T SNP in both alleles could be used as a screen to exclude potentially poor responders to 17-AAG treatment at low dosages.
    Full-text · Article · May 2014 · BMC Cancer
  • Nisha Nisha · Parvesh Singh · Denver T. Hendricks · Krishna Bisetty · Vipan Kumar
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    ABSTRACT: beta-Lactam-synthon-interceded synthesis of isatin-imidazolidine-2-thione conjugates was carried out via base-assisted intermolecular amidolysis of 3-isothiocyanato-2-azetidinones with C-5 substituted isatins. The observed enolization in the assigned structure of the conjugates was validated using molecular dynamic (MD) simulations performed under explicit solvent conditions. The synthesized scaffolds were also evaluated for their cytotoxic profiles against the oesophageal cancer cell line WHCO1.
    No preview · Article · Feb 2014 · ChemInform
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    ABSTRACT: Oesophageal cancer is one of the most common causes of cancer-related deaths in South African black males. The limited efficacy of chemotherapeutic agents to treat this disease has prompted a search for potential new chemical entities with anticancer properties. We report here on the evidence for anti-oesophageal cancer activity in the methanolic extracts of five species of sponges dredged from a depth of approximately 100 m in the vicinity of Marion Island in the Southern Ocean during the autumn of 2004.
    Full-text · Article · Jan 2014 · South African Journal of Science
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    ABSTRACT: A series of mono- and multimeric 4-amino-7-chloroquinoline and ferrocenyl thioureas have been prepared by the reaction of a 7-chloroquinoline methyl ester and a ferrocenylimine methyl ester with various amines. These compounds were characterized using standard spectroscopic and analytical techniques. The compounds were evaluated against the NF54 (CQ-sensitive) and Dd2 (CQ-resistant) strains of Plasmodiumfalciparum. The quinoline compounds show enhanced activity compared to the ferrocene compounds against this parasite. Compound 5 displays the most promising activity against the NF54 strain. Compounds 5 and 6 are effective at inhibiting β-hematin formation perhaps due to an increased number of quinoline moieties. The trimeric (12) and tetrameric (13) ferrocenyl compounds also inhibit β-hematin formation, albeit to a lesser degree compared to the quinoline thioureas. The compounds were also screened against the G3 strain of Trichomonasvaginalis and here the ferrocene-containing compounds show a slightly higher parasite growth inhibition compared to the quinoline thioureas. The quinoline compounds were also found to be more cytotoxic compared to the ferrocenyl compounds. Compound 6 displays good cytotoxicity against WHCO1 oesophageal cancer cells.
    Full-text · Article · Aug 2013 · European Journal of Medicinal Chemistry
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    ABSTRACT: Naphthoquinones have been found to have a wide range of biological activities, including cytotoxicity to cancer cells. The secondary metabolites lapachol, α- and β-lapachone and a series of 25 related synthetic 1,4-naphthoquinones were screened against the oesophageal cancer cell line (WHCO1). Most of the compounds exhibited enhanced cytotoxicity (IC(50) 1.6-11.7 μM) compared to the current drug of choice cisplatin (IC(50) = 16.5 μM). This study also established that the two new synthetic halogenated compounds 12a and 16a (IC(50) = 3.0 and 7.3 μM) and the previously reported compound 11a (IC(50) = 3.9 μM), were non-toxic to NIH3T3 normal fibroblast cells. Cell death of oesophageal cancer cells by processes involving PARP cleavage caused by 11a was shown to be associated with elevated c-Jun levels, suggesting a role for this pathway in the mechanism of action of this cohort of naphthoquinone compounds.
    Full-text · Article · Jan 2013 · European Journal of Medicinal Chemistry
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    ABSTRACT: Two silicon-containing analogues (1, 2) of chloroquine, modified in the lateral side chain with organosilicon moieties, were synthesized. Compounds 1 and 2 were further reacted with dinuclear half-sandwich transition metal precursors [Ru(Ar)(μ-Cl)Cl] 2 (Ar = η 6 -p-i PrC 6 H 4 Me; η 6 -C 6 H 6 ; η 6 -C 6 H 5 OCH 2 CH 2 OH), [Rh(COD)(μ-Cl)] 2 , and [RhCp*(μ-Cl)Cl] 2 , to yield a series of neutral mononuclear Ru(II), Rh(I), and Rh(III) silicon-aminoquinoline complexes (3−12). Compounds 1 and 2 act as monodentate donors that coordinate to the transition metals via the quinoline nitrogen of the aminoquinoline scaffold. All the compounds were characterized using various analytical and spectroscopic techniques, and the molecular structures of compounds 2 and 11 were elucidated by single-crystal X-ray diffraction analysis. Furthermore, the in vitro pharmacological activities of compounds 1−12 were established against chloroquine-sensitive (NF54) and chloroquine-resistant (Dd2) strains of the malarial parasite Plasmodium falciparum and against the pathogenic bacterium Mycobacterium tuberculosis H 37 R v , as well as an esophageal (WHCO1) cancer cell line.
    Full-text · Dataset · Dec 2012
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    ABSTRACT: N-myc downstream regulated gene 1 (NDRG1/Cap43/Drg-1) has previously been shown to be dysregulated in esophageal squamous cell carcinoma (ESCC). In this study, we investigated the role of NDRG1 in the neoplastic progression of ESCC using ectopic gain-of-function and loss-of-function approaches. Stable transfectants of the KYSE30 ESCC cell line with altered NDRG1 levels were generated by lentiviral transduction. Although no measurable effects on in vitro cell proliferation were observed with altered NDRG1 expression, the ectopic overexpression of NDRG1 was positively linked to recognized markers of metastasis, angiogenesis and apoptotic evasion. Accordingly, in the nude mouse xenograft model system, NDRG1 overexpression promoted the in vivo growth of KYSE30 derived xenografts, which could be attributed to the reduced apoptotic and enhanced angiogenic activities associated with this gene. These processes were mediated in part by increased NFκB activity in NDRG1 overexpressing cells. Nevertheless, no significant phenotypic changes were observed in response to NDRG1 knock-down, suggesting that this gene might not be essential for the neoplastic progression of ESCC. Taken together, our results suggest that NDRG1 may play positive but dispensable roles in the progression of esophageal squamous cell carcinoma.
    Full-text · Article · Nov 2012 · Cancer biology & therapy
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    ABSTRACT: A convenient and unprecedented synthesis of functionally enriched octahydroindole-based scaffolds has been developed via inter- and intra-molecular amidolysis of C-3 functionalized β-lactams. The cytotoxic evaluation on oesophageal cancer cell line WHCO1 has revealed 7d as the most potent of the test compounds exhibiting an IC(50) value of 12.97μM. The developed strategy further assumes significance as it entails the preparation of highly functionalized indoles without the aid of transition metal catalysis or pre-functionalization of substrates.
    Full-text · Article · Nov 2012 · European Journal of Medicinal Chemistry
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    Haleden Chiririwa · John R Moss · Denver Hendricks · Reinout Meijboom
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    ABSTRACT: The title compound C(18)H(16)N(2)S(2), crystallizes with two independent half-mol-ecules in the asymmetric unit, in one of which the thio-phene rings are disordered in a 0.67:0.33 ratio. Each independent mol-ecule lies across a crystallographic centre of symmetry. The dihedral angle between central (half) benzene ring and the thiophene ring is 11.82°.
    Full-text · Article · Nov 2012 · Acta Crystallographica Section E Structure Reports Online
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    ABSTRACT: a b s t r a c t The reactions of iminophosphine ligands with [PtCl 2 (COD)], [PtCl 2 (DMSO) 2 ], and [Au(tht)Cl] has been inves-tigated. The new platinum(II) and gold(I) complexes were characterised using elemental analysis, electro-spray ionisation-mass spectrometry (ESI-MS), NMR (1 H and 31 P) and IR spectroscopy and X-ray diffraction studies. In vitro cytotoxic study results show that platinum and gold complexes block the proliferation of WHCO1 and KYSE450 cell lines with an IC 50 range of 2.16–9.47 lM.
    Full-text · Dataset · Mar 2012
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    ABSTRACT: To determine the association between serum levels of growth-related gene product β (GROβ) and clinical parameters in esophageal squamous cell carcinoma (ESCC). Using enzyme-linked immunosorbent assay, serum GROβ levels were measured in ESCC patients (n = 72) and healthy volunteers (n = 83). The association between serum levels of GROβ and clinical parameters of ESCC was analyzed statistically. The serum GROβ levels were much higher in ESCC patients than in healthy controls (median: 645 ng/L vs 269 ng/L, P < 0.05). Serum GROβ levels were correlated positively with tumor size, lymph node metastasis, and tumor-node-metastasis (TNM) staging, but not with gender or the histological grade of tumors in ESCC patients. The sensitivity and specificity of the assay for serum GROβ were 73.61% and 56.63%, respectively. GROβ may function as an oncogene product and contribute to tumorigenesis and metastasis of ESCC.
    Full-text · Article · Jun 2011 · World Journal of Gastroenterology
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    ABSTRACT: A series of mono- and dinuclear (η6-arene) ruthenium(II) complexes were prepared by reaction of thiosemicarbazone ligands derived from benzaldehyde and ruthenium(II) precursors of the general formula [Ru(η6-arene)(μ-Cl)Cl]2, where arene=p-iPrC6H4Me or C6H5C3H6COOH. These complexes were characterized by NMR and IR spectroscopy, ESI-mass spectrometry and elemental analysis. The molecular structure of the mononuclear p-cymene complex was determined by X-ray diffraction analysis, revealing a pseudo-tetrahedral piano stool conformation and a bidentate N,S coordination mode of the thiosemicarbazone ligand. The complexes and ligands were evaluated for their in vitro cytotoxicity against the WHCO1 oesophageal cancer cell line.
    Full-text · Article · Jun 2011 · Inorganic Chemistry Communications
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    Qiaomei Dong · Jinqiang Zhang · Denver T Hendricks · Xiaohang Zhao
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    ABSTRACT: Cisplatin is one of the most widely used chemotherapeutic agents employed for treatment of a wide variety of solid tumors, including human esophageal squamous cell carcinoma (ESCC). However, a major limitation of cisplatin-based chemotherapy of ESCC is the rather low-effective rate. Understanding the molecular events of limited efficacy of cisplatin-based chemotherapy of ESCC could lead to strategies resulting in improved therapeutic benefits. The CXC chemokine family has been reported to be related to inflammatory reaction, injure recovery, cell proliferation, apoptosis and even to be involved in the regulation of chemotherapeutic agent-induced apoptosis. CXCL2 chemokine, also known as GROβ (growth-related gene product β), belongs to the CXC chemokine group. The known functions of GROβ are related to attracting neutrophils to sites of inflammation, modulation of the neurotransmitter release, cell proliferation and apoptosis. However, little is known about the relationship between GROβ and chemotherapeutic agent-induced apoptosis. This study was designed to provide insights into the possible role of GROβ in the regulation of cisplatin-induced apoptosis in ESCCs. We report here that inhibition of expression of GROβ can decrease cisplatin-induced apoptosis in WHCO1 cells. EGR1 is a downstream factor regulated by GROβ. Silencing expression of EGR1 can also decrease cisplatin-induced apoptosis in WHCO1 cells. The activation of caspase 9 was delayed in cells in which GROβ and EGR1 were knocked down after cisplatin treatment. All these results indicate that GROβ and its downstream factor EGR1 are involved in regulating cisplatin-induced apoptosis in WHCO1 cells, and during this process the intrinsic apoptotic pathway is activated. It may be useful to examine the expression levels of GROβ and EGR1 in ESCC patients to select those likely to respond well to cisplatin.
    Full-text · Article · Apr 2011 · Oncology Reports
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    Haleden Chiririwa · John R Moss · Hong Su · Denver Hendricks · Reinout Meijboom
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    ABSTRACT: In the title compound, C(22)H(22)N(4), the centroid of the benzene ring is located on an inversion centre. The dihedral angle between the benzene and pyridine rings is 10.94 (5)°. The crystal structure displays weak inter-molecular C-H⋯N hydrogen bonding and C-H⋯π inter-actions.
    Full-text · Article · Apr 2011 · Acta Crystallographica Section E Structure Reports Online
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    ABSTRACT: Five known (1, 2, 4, 6 and 7) halogenated monoterpenes together with 1Z,3R∗,4S∗,5E,7Z)-1-bromo-3,4,8-trichloro-7-(dichloromethyl)-3-methylocta-1,5,7-triene (3) and (3R∗,4S∗)-3,4,6,7-tetrachloro-3,7-dimethyl-octen-1-ene (5) were isolated from the red macroalga Plocamium suhrii and their structures deduced from their spectroscopic data. The seven compounds from P. suhrii together with five related compounds from Plocamium cornutum have been evaluated for their cytotoxic effects on an esophageal cancer cell line (WHCO1). Compounds 1-6 showed greater cytotoxicity in this assay as compared to the known anticancer drug cisplatin.
    Full-text · Article · Mar 2011 · Phytochemistry
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    Tameryn Stringer · Denver T Hendricks · Hajira Guzgay · Gregory S Smith
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    ABSTRACT: a b s t r a c t A series of di-and trithiosemicarbazone ligands as well as their Pd(II) and Pt(II) 1,3,5-triaza-7-phospha-adamantane (PTA) complexes have been synthesised using templated reactions between various substi-tuted salicylaldimine thiosemicarbazone ligands and metal precursors of the general formula cis-[M(PTA) 2 Cl 2 ], where M = Pd or Pt. Characterization of these complexes was achieved using various ana-lytical and spectroscopic techniques: elemental analysis, ESI-MS, FT-IR, and NMR (1 H, 13 C{ 1 H} and 31 P{ 1 H}) spectroscopy. The data revealed tridentate (O–N–S) coordination of the thiosemicarbazone moi-eties via the imine nitrogen, thiolato sulfur and phenolic oxygen to each metal center. In vitro biological evaluation of selected compounds was conducted against WHCO1 oesophageal cancer cells. Some of the multimeric compounds display some promising biological activity.
    Full-text · Article · Jan 2011 · Polyhedron

Publication Stats

1k Citations
184.58 Total Impact Points

Institutions

  • 2002-2015
    • University of Cape Town
      • Division of Medical Biochemistry
      Kaapstad, Western Cape, South Africa
  • 2006-2007
    • Rhodes University
      • Department of Chemistry
      Grahamstad, Eastern Cape, South Africa
  • 2000
    • National Institutes of Health
      • Section on Molecular and Cell Biology
      Maryland, United States
  • 1999
    • University of North Carolina at Chapel Hill
      • Department of Pathology and Laboratory Medicine
      North Carolina, United States
  • 1997-1999
    • National Cancer Institute (USA)
      • Cell and Cancer Biology Branch
      Maryland, United States