Denver T Hendricks

Guru Nanak Dev University, Amritsar, Punjab, India

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Publications (34)78.16 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: The anion derived from isatins (I) reacts with isocyanates (II) to form imidazolidine-2-thiones (III), some of which show significant cytotoxic activity against the oesophageal cancer cell line WHCO1.
    ChemInform 02/2014; 45(5).
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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.
    South African Journal of Science 01/2014; · 0.84 Impact Factor
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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.
    European journal of medicinal chemistry 08/2013; 69C:90-98. · 3.27 Impact Factor
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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.
    European journal of medicinal chemistry 01/2013; 62C:98-110. · 3.27 Impact Factor
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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.
    Cancer biology & therapy 11/2012; 14(2). · 3.29 Impact Factor
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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.
    European journal of medicinal chemistry 11/2012; 58C:513-518. · 3.27 Impact Factor
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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°.
    Acta Crystallographica Section E Structure Reports Online 11/2012; 68(Pt 11):o3137. · 0.35 Impact Factor
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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.
    World Journal of Gastroenterology 06/2011; 17(21):2658-62. · 2.55 Impact Factor
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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.
    Acta Crystallographica Section E Structure Reports Online 04/2011; 67(Pt 4):o921. · 0.35 Impact Factor
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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.
    Phytochemistry 03/2011; 72(8):769-72. · 3.05 Impact Factor
  • 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.
    Oncology Reports 01/2011; 25(4):1031-7. · 2.30 Impact Factor
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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.
    Inorganic Chemistry Communications - INORG CHEM COMMUN. 01/2011; 14(6):956-960.
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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.
    Polyhedron. 01/2011;
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    Berichte der deutschen chemischen Gesellschaft 06/2010; 2010(22):3520 - 3528. · 2.94 Impact Factor
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    ABSTRACT: Although early growth response-1 (EGR-1) has been shown as a key transcription factor in controlling cell growth, proliferation, differentiation, and angiogenesis, its role in the development of esophageal cancer is poorly understood despite the high frequency of this disease in many parts of the world. Here, immunohistochemistry showed that EGR-1 is overexpressed in 80% of esophageal tumor tissues examined. Furthermore, EGR-1 is constitutively expressed in all esophageal cancer cell lines analyzed. Esophageal squamous carcinoma WHCO1 cells stably transfected with EGR-1 short hairpin RNA displayed a 55% reduction in EGR-1 protein levels, 50% reduction in cell proliferation, a 50% reduction in cyclin-dependent kinase 4 levels, and a 2-fold induction in p27(Kip1) levels associated with a G(2)-M cell cycle arrest. EGR-1 knockdown also caused a marked induction in IkappaBalpha expression, an effect also observed in GRObeta RNA interference-expressing WHCO1 cells, because EGR-1 lies downstream of GRO/CXCR2 signaling. Furthermore, p65 mRNA levels were also reduced in cells treated with either short hairpin RNA EGR-1 or small interfering RNA EGR-1. Immunohistochemical analysis indicated that p65 is elevated in 78% (n = 61) of esophageal tumor sections analyzed. Moreover, nuclear factor-kappaB inhibition with either sodium salicylate or p65 RNA interference led to a significant reduction in GROalpha and GRObeta expression. These results indicate that EGR-1 and nuclear factor-kappaB mediate GRO/CXCR2 proliferative signaling in esophageal cancer and may represent potential target molecules for therapeutic intervention.
    Molecular Cancer Research 06/2009; 7(5):755-64. · 4.35 Impact Factor
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    ABSTRACT: The Karyopherin proteins are involved in nucleo-cytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest they are important in nuclear envelope component assembly, mitosis and replication. Since these are all critical cellular functions, alterations in the expression of the Karyopherins may have an impact on the biology of cancer cells. In this study, we examined the expression of the Karyopherins, Crm1, Karyopherin beta1 (Kpnbeta1) and Karyopherin alpha2 (Kpnalpha2), in cervical tissue and cell lines. The functional significance of these proteins to cancer cells was investigated using individual siRNAs to inhibit their expression. Microarrays, quantitative RT-PCR and immunofluorescence revealed significantly higher expression of Crm1, Kpnbeta1 and Kpnalpha2 in cervical cancer compared to normal tissue. Expression levels were similarly elevated in cervical cancer cell lines compared to normal cells, and in transformed epithelial and fibroblast cells. Inhibition of Crm1 and Kpnbeta1 in cancer cells significantly reduced cell proliferation, while Kpnalpha2 inhibition had no effect. Noncancer cells were unaffected by the inhibition of Crm1 and Kpnbeta1. The reduction in proliferation of cancer cells was associated with an increase in a subG1 population by cell cycle analysis and Caspase-3/7 assays revealed increased apoptosis. Crm1 and Kpnbeta1 siRNA-induced apoptosis was accompanied by an increase in the levels of growth inhibitory proteins, p53, p27, p21 and p18. Our results demonstrate that Crm1, Kpnbeta1 and Kpnalpha2 are overexpressed in cervical cancer and that inhibiting the expression of Crm1 and Kpnbeta1, not Kpnalpha2, induces cancer cell death, making Crm1 and Kpnbeta1 promising candidates as both biomarkers and potential anticancer therapeutic targets.
    International Journal of Cancer 12/2008; 124(8):1829-40. · 6.20 Impact Factor
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    ABSTRACT: A reinvestigation of extracts of the endemic South African intertidal limpet Trimusculus costatus yielded the known labdane diterpenes 6beta,7alpha-diacetoxylabda-8,13 E-dien-15-ol ( 1) and 2alpha,6beta,7alpha-triacetoxylabda-8,13 E-dien-15-ol ( 2) and three new metabolites, 6beta,7alpha,15-triacetoxylabda-8,13 E-diene ( 3), 3alpha,11-dihydroxy-9,11-seco-cholest-4,7-dien-6,9-dione ( 4), and cholest-7-en-3,5,7-triol ( 5). Chiral derivatization and X-ray analysis were used to confirm the labdane absolute configuration of 2. Compounds 1, 2 and 4 exhibited moderate activity (3-25 microM) against the WHCO1 human esophageal cancer cell line.
    Journal of Natural Products 04/2008; 71(3):420-5. · 3.29 Impact Factor
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    ABSTRACT: Several studies have detected human papilloma virus (HPV) DNA in squamous cell carcinoma of the oesophagus (OSCC). In this study, we analysed OSCC specimens from 114 patients for the presence of HPV DNA, and p53 and p73 expression. HPV DNA was detected in 44.7% of cases, with the low risk HPV11 occurring most frequently. p53 and p73 expression was detected in 70% and 61.4% of cases, respectively. There was no correlation between expression of p53, p73 or HPV infection and tumour grade, or between p53 expression and the presence of HPV DNA. There was, however, significant correlation between p73 expression and the presence of HPV DNA (p<0.01) and p53 and p73 co-expression (p<0.001), as well as co-expression of p53 and p73 with HPV status (p<0.05). These data support previous studies suggesting a role for HPV infection in OSCC and also indicate that HPV infection and p53 and p73 overexpression are not mutually exclusive. In addition, the data implicate a role for p73 in OSCC and suggest a complex interaction between p53, p73 and HPV in the aetiology of the disease.
    Virology 01/2008; 369(1):182-90. · 3.37 Impact Factor
  • ChemInform 01/2008; 39(25).
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    ABSTRACT: Marine invertebrates, algae, and microorganisms are prolific producers of novel secondary metabolites. Some of these secondary metabolites have the potential to be developed as chemotherapeutic agents for the treatment of a wide variety of diseases, including cancer. We describe here the mechanism leading to apoptosis of esophageal cancer cell lines in the presence of triprenylated toluquinones and toluhydroquinones originally isolated from the Arminacean nudibranch Leminda millecra. Triprenylated toluquinone-induced and toluhydroquinone-induced cell death is mediated via apoptosis after a cell cycle block. Molecular events include production of reactive oxygen species (ROS), followed by induction and activation of c-Jun (AP1) via c-Jun-NH2-kinase-mediated and extracellular signal-regulated kinase-mediated pathways. Partial resistance to these compounds could be conferred by the ROS scavengers Trolox and butylated hydroxyanisol, a c-Jun-NH2-kinase inhibitor, and inhibition of c-Jun with a dominant negative mutant (TAM67). Interestingly, the levels of ROS produced varied between compounds, but was proportional to the ability of each compound to kill cells. Because cancer cells are often more susceptible to ROS, these compounds present a plausible lead for new antiesophageal cancer treatments and show the potential of the South African marine environment to provide new chemical entities with potential clinical significance.
    Molecular Cancer Therapeutics 10/2007; 6(9):2535-43. · 5.60 Impact Factor

Publication Stats

211 Citations
78.16 Total Impact Points

Institutions

  • 2014
    • Guru Nanak Dev University
      • Department of Chemistry
      Amritsar, Punjab, India
  • 2005–2013
    • Rhodes University
      • • Department of Chemistry
      • • Faculty of Pharmacy
      Grahamstown, Province of Eastern Cape, South Africa
  • 2004–2013
    • University of Cape Town
      • • Department of Chemistry
      • • Division of Medical Biochemistry
      • • Institute of Infectious Disease & Molecular Medicine (IIDMM)
      • • Faculty of Health Sciences
      Cape Town, Province of the Western Cape, South Africa