33 research outputs found
Biological Evaluation of Platinum(II) Sulfonamido Complexes: Synthesis, Characterization, Cytotoxicity, and Biological Imaging
No full textPlatinum-based compounds are actively used in clinical trials as anticancer agents. In this study, two novel platinum complexes, (C1 = [PtCl(2)(N(SO(2)quin)dpa)], C2 = [PtCl(2)(N(SO(2)azobenz)dpa)]) containing quinoline and azobenzene appended dipicolylamine sulfonamide ligands were synthesized in good yield. The singlet attributable to methylene CH(2) protons of the ligands of C1 and C2 appears as two doublets in (1)H NMR spectra, which confirms the presence of magnetically nonequivalent protons upon coordination to platinum. Structural data of N(SO(2)quin)dpa (L1), N(SO(2)azobenz)dpa (L2) and PtCl(2)(N(SO(2)quin)dpa) confirmed the formation of the desired compounds. Time-dependent density functional theory calculations suggested that the excitation of L1 show quin-unit-based π⟶π(∗) excitations (i.e., ligand-centered charge transfer, LC), while C1 shows the metal-ligand-to-ligand charge-transfer (MLLCT) character. L1 displays intense fluorescence from the (1)LC excited state, while C1 gives phosphorescence from the (3)LC state. Mammalian cell toxicity of ligands and complexes was assessed with NCI–H292 nonsmall-cell lung cancer cells. Further, C1 and C2 showed significantly low IC(50) values compared with N(SO(2)azobenz)dpa and PtCl(2)(N(SO(2)quin)dpa). Fluorescence imaging data of both ligands and complexes revealed the potential fluorescence activity of these compounds for biological imaging. All four compounds are promising novel candidates that can be further investigated on their usage as potential anticancer agents and cancer cell imaging agents
Modulation of apoptosis in human hepatocellular carcinoma (HepG2 cells) by a standardized herbal decoction of <it>Nigella sativa </it>seeds, <it>Hemidesmus indicus </it>roots and <it>Smilax glabra </it>rhizomes with anti- hepatocarcinogenic effects
No full textAbstract Background A standardized poly-herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabra rhizomes used traditionally in Sri Lanka for cancer therapy has been demonstrated previously, to have anti-hepatocarcinogenic potential. Cytotoxicity, antioxidant activity, anti-inflammatory activity, and up regulation of p53 and p21 activities are considered to be some of the possible mechanisms through which the above decoction may mediate its anti-hepatocarcinogenic action. The main aim of the present study was to determine whether apoptosis is also a major mechanism by which the decoction mediates its anti-hepatocarcinogenic action. Methods Evaluation of apoptosis in HepG2 cells was carried out by (a) microscopic observations of cell morphology, (b) DNA fragmentation analysis, (c) activities of caspase 3 and 9, as well as by (d) analysis of the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins associated with cell death. Results The results demonstrated that in HepG2 cells, the decoction can induce (a) DNA fragmentation and (b) characteristic morphological changes associated with apoptosis (nuclear condensation, membrane blebbing, nuclear fragmentation and apoptotic bodies). The decoction could also, in a time and dose dependent manner, up regulate the expression of the pro-apoptotic gene Bax and down regulate expression of anti-apoptotic Bcl-2 gene (as evident from RT-PCR analysis, immunohistochemistry and western blotting). Further, the decoction significantly (p Conclusions Overall findings provide confirmatory evidence to demonstrate that the decoction may mediate its reported anti-hepatocarcinogenic effect, at least in part, through modulation of apoptosis.</p
Synthesis, characterization and biological evaluation of dipicolylamine sulfonamide derivatized platinum complexes as potential anticancer agents
No full textThree new Pt complexes, [PtCl(N(SO(2-nap))dpa)], [PtCl(N(SO(1-nap))dpa)] and [PtCl(N(SOpip)dpa)], containing a rare 8-membered ring were synthesized in good yield and high purity by utilizing the ligands N(SO(2-nap))dpa, N(SO(1-nap))dpa and N(SOpip)dpa, which contain a dipicolylamine moiety. Structural studies of all three complexes confirmed that the ligands are bound in a bidentate mode Pt-N bonds forming a rare 8-membered ring. The intense fluorescence displayed by the ligands is quenched upon coordination to Pt. According to time dependent density functional theory (TDDFT) calculations, the key excitations of N(SO(2-nap))dpa and [PtCl(N(SO(1-nap))dpa)] involve the 2-nap-ligand-centered π → π* excitations. While all six compounds have shown antiproliferative activity against human breast cancer cells (MCF-7), the N(SOpip)dpa and N(SO(2-nap))dpa ligands and [PtCl((NSOpip)dpa)] complex have shown significantly high cytotoxicity, directing them to be further investigated as potential anti-cancer drug leads
Effect of Standardized Decoction of Nigella sativa Seed, Hemidesmus indicus Root and Smilax glabra Rhizome on the Expression of p53 and p21 Genes in Human Hepatoma Cells (HepG2) and Mouse Liver with Chemically-Induced Hepatocarcinogenesis
No full textPurpose: To evaluate in vitro (using human hepatoma HepG2 cells) and in
vivo (using mouse liver with diethlynitrosamine (DEN)-induced
hepatocarcinogenesis) effect of a standardized decoction on the
expression of p53 (tumour suppressor) and p21 (cyclin kinase inhibitor)
genes with the long-term goal of developing the formulation into a
globally acceptable therapy for hepatocellular carcinoma (HCC).
Methods: The effect of the decoction on (a) mRNA and (b) protein
expression of p53 and p21 genes in HepG2 cells and mouse livers with
DEN-induced early hepatocarcinogenesis were evaluated by (a) reverse
transcription PCR (RT-PCR) and (b) immunohistochemical and Western blot
analysis, respectively. Results: The results demonstrated that the
decoction significantly (p <0.001) enhanced the expression of p53
and p21 genes in a time- and dose-dependent manner in HepG2 cells. A
dose of 75 μg/ml significantly increased p53 mRNA at 24 and 48 h
and p21 mRNA at 12, 24, 48 h of incubation with the decoction (p
<0.01). Induction of hepatocarcinogenesis in mice significantly
increased hepatic expression of both p53 and p21 compared to distilled
water control (p <0.001), while treatment with the decoction further
enhanced expression of both genes in DEN-induced hepatocarcinogenesis
(p <0.01). Conclusion: Overall, the findings demonstrate that the
decoction may mediate its reported antihepatocarcinogenic effect, at
least in part, through the modulating activities of genes involved in
tumour suppression and cell cycle arrest
Synthesis, Characterization and Remarkable Anticancer Activity of Rhenium Complexes Containing Biphenyl Appended NNN Donor Sulfonamide Ligands
No full textNeutral and cationic rhenium complexes provide both hydrophilic as well as hydrophobic properties due to the robustness of the tridentate ligand system of biphenyl appended dipicolylamine (N(SO2bip)dpa) and diethylenetriamine (N(SO2bip)dienH) coordinated to the [Re(CO)3]+ core, hold immense potential for the development of metal based anticancer drugs. This was achieved by the synthesis of two ligands (L1: N(SO2bip)dpa and L2: (N(SO2bip)dienH) and their corresponding Re complexes (C1: [Re(CO)3(N(SO2bip)dpa)]PF6 and C2: [Re(CO)3(N(SO2bip)dien)] in good yield and high purity. All four compounds were characterized by 1H NMR, UV-Vis, FTIR spectroscopies and L1, also by single crystal X-ray diffraction. The methylene protons observed as a singlet at (4.59 ppm) in a 1H NMR spectrum of L1 appear as two doublets (5.66 and 4.65 ppm) in the spectrum of C1. The appearance of NH signals at 3.48, 5.17 and 6.69 ppm in the 1H NMR spectrum of C2 confirm the coordination of L2 with Re. The stretching vibration frequencies depicted by the S-N bond at 923 cm-1 for L1 appear towards lower frequencies (821 cm-1) in an FTIR spectrum of C1, while the S-N bond at 943 cm-1 for L2 appears towards higher frequencies (968 cm-1) in C2. In silico assessment of drug likeliness revealed zero violations demonstrating a high likeliness of the ligands to be successful as drug leads. All four compounds have shown very low IC50 values against non-small cell lung cancer cells (NCI-H292). Therefore, L1, C1, L2 and C2 are promising novel compounds that can be further investigated as potential anticancer agents.
Keywords: Rhenium Tricarbonyl, Sulfonamide, Anticancer, Fluorescence
Screening of five Sri Lankan endemic plants for anti-cancer effects on breast cancer stem cells isolated from MCF-7 and MDA-MB-231 cell lines
No full textPurpose: To screen selected endemic plants grown in Sri Lanka on breast cancer stem cells (bCSCs) for their anti-cancer propertiesMethods: Breast-CSCs expressing CD24-/CD44+ surface markers were isolated from MDA-MB-231 cells by magnetic-assisted cell sorting method and validated using flow cytometry. A panel of forty extracts from barks and leaves of Doona nervosa, Garcinia quaesita, Garcinia zeylanica, Memecylon rostratum and Schumacheria castaneifolia were obtained by sequential solvent extraction and tested on bCSC-mammospheres derived from MDA-MB-231 and MCF-7 cells and normal mammary epithelial (MCF-10A) cells. Proliferation and cell stemness were analyzed using WST-1 cell proliferation assay and alkaline phosphatase assay.Results: Hexane and chloroform extracts of G. zeylanica and G. quaesita barks showed dosedependent reduction in proliferation and stemness in both bCSCs tested with less effect on MCF-10A cells. Hexane, chloroform and ethyl acetate extracts of S. castaneifolia bark selectively inhibited mammospheres of triple negative bCSCs cells.Conclusion: This study demonstrates that the non-polar extracts of G. zeylanica and G. quaesita, S. castaneifolia barks inhibit the proliferation of bCSCs of triple negative and estrogen-progesterone positive breast cancers. Findings of the present study may useful for developing a future anti-cancer therapeutics which can target bCSCs.Keywords: Cancer stem cells, Garcinia zeylanica, Garcinia quaesita, Schumacheria castaneifolia, Mammosphere
Secretory phospholipase A2 inhibitory activity in Tragia hispida: A novel and promising therapeutic agent for dengue fever
No full textBackground: Tragia hispida, is widely used in Sri Lankan traditional ayurvedic medicine for the treatment of fever and internal bleeding. Dengue hemorrhagic fever (DHF) is a severe form of dengue characterized by vascular leakage and potential fatality. Secretory phospholipase A2 (sPLA2), an inflammatory enzyme, plays a critical role in producing platelet-activating factor (PAF), a key mediator of vascular leak. Elevated sPLA2 activity has been linked to the progression of DHF. Purpose: This study aimed to evaluate the sPLA2 inhibitory activity of T. hispida plant extracts with bee venom and dengue patient serum sPLA2. Methods: sPLA2 inhibitory activity of different fractions of the plant was evaluated by a commercially available sPLA2 assay kit compared to the inhibition caused by the commercially available sPLA2 inhibitor CAY 10590. The butanol soluble fraction (THB) of the aqueous extract of Tragia hispida was characterized by TLC and HPLC. Results: Both the aqueous extract (THA) and THB of T. hispida demonstrated sPLA2 inhibition levels comparable to positive control, CAY 10590. At concentrations of 100 µg/ ml and 200 µg/ ml, THB inhibited sPLA2 activity of bee venom by 59.3 % and 84.9 % respectively. Furthermore, THB exhibited significant inhibition of sPLA2 activity in human serum from dengue patients (n = 31, p < 0.0001) than that exhibited by CAY 10590. Conclusions: These findings highlight the potential of T. hispida, particularly THB, as a promising therapeutic agent for dengue fever by inhibiting sPLA2 activity
Sustainable development of deltas: An international conference
No full textPREFACE Prince Claus of The Netherlands PROGRAMME \u95 Contents \u95 Introduction by Anne van Urk \u95 Conference programme \u95 Characteristics of the delta countries SUMMARIES OF KEYNOTES Future role and position of Public Works (Gerrit Blom) Sustainable development of deltas (lsmael Serageldin) The bank's approach to sustainable development of deltas: experience and lessons (Peter Sullivan) Public participation: risks and opportunities (L.E. Susskind) Public works: institutional agreement and social participation (Eduardo A. Duhalde) Technical innovation: can technology provide solutions (J. Blaauwendraad) What should Public Works Departments contribute to sustainable development in our common future (K. Topfer) Skills required by Public Works Departments in the 21st century (M.A.H. Abu-Zeid) COUNTRY/DELTA POSITION PAPERS China - Government of China Philippines - Samuel Costodio Vietnam: Red River Delta looking forward - Vu Trong Hong and Le Kim Truyen Thailand: The Chao Praya Delta and the development of Bangkok Metropolitan Region -Siripong Hungspreug, Ruengsak Suthakavatin, and Ksemsan Suwamarat Indonesia: Brantas delta and its development - Ministry of Public Works Bangladesh - A.T.M. Shamsul Huda Sri-Lanka: eroding coastlines, infrastructure and Ecosystem-based special area management - H. Nissanka R. Perera, and Jayampathy Samarakoon India: Indian economy and sustainable development - O.P. Sharma Pakistan: Indus delta - Malik Mohammad Saeed Khan Russia: St. Petersburg enters the 21st century - Yury V. Antonov Egypt: Overview of Egypt's Nile valley and delta - Abdei-Rahman M. Shalaby, Mona El-Kady, and Safwat Abdei-Dayem The Netherlands: How to continue the sustainable development in The Netherlands? Joost de Jong, Pieter Huisman, Henk Pauwels and Roxanne Powel Surinam - Ministry of Public Works, et al. Argentina: The Rfo de la Plata delta in the Argentine Republic - Presidency of the Nation, et al. VISIONS Skills and strategies needs of 'Public Works Departments': a view from the UN/Economic - UN/ECE Commission for Europe with a focus on an environmentally sustainable development of coastal areas Public Works gearing up for the 21st century - UNESCO UNIDO concept of Integrated Coastal Zone - UNIDO Management as a toolbox for environmentally sustainable development in deltas: The view of the World Meteorological Organization - WMO Capacities and skills in support of public health, the perspective of the World Health Organization - WHO The vision of the water boards - Association of Water Boards Orientability in a world in transformation - Delft Geotechnics Engineers in Public Works - KIVI Public Works in the 21st century - LWI Wanted: Support for the sustainable development of deltas - NCDO DIGITAL DELTAS for the 21st century - TNO Role and vision of contractors in coastal zone development - VBKOKWP-collectio
Modulation of expression of heat shock proteins and apoptosis by Flueggea leucopyrus (Willd) decoction in three breast cancer phenotypes
No full textEffect of Standardized Decoction of Nigella sativa Seed, Hemidesmus indicus Root and Smilax glabra Rhizome on the Expression of p53 and p21 Genes in Human Hepatoma Cells (HepG2) and Mouse Liver with Chemically-Induced Hepatocarcinogenesis
No full textPurpose: To evaluate in vitro (using human hepatoma HepG2 cells) and in
vivo (using mouse liver with diethlynitrosamine (DEN)-induced
hepatocarcinogenesis) effect of a standardized decoction on the
expression of p53 (tumour suppressor) and p21 (cyclin kinase inhibitor)
genes with the long-term goal of developing the formulation into a
globally acceptable therapy for hepatocellular carcinoma (HCC).
Methods: The effect of the decoction on (a) mRNA and (b) protein
expression of p53 and p21 genes in HepG2 cells and mouse livers with
DEN-induced early hepatocarcinogenesis were evaluated by (a) reverse
transcription PCR (RT-PCR) and (b) immunohistochemical and Western blot
analysis, respectively. Results: The results demonstrated that the
decoction significantly (p <0.001) enhanced the expression of p53
and p21 genes in a time- and dose-dependent manner in HepG2 cells. A
dose of 75 μg/ml significantly increased p53 mRNA at 24 and 48 h
and p21 mRNA at 12, 24, 48 h of incubation with the decoction (p
<0.01). Induction of hepatocarcinogenesis in mice significantly
increased hepatic expression of both p53 and p21 compared to distilled
water control (p <0.001), while treatment with the decoction further
enhanced expression of both genes in DEN-induced hepatocarcinogenesis
(p <0.01). Conclusion: Overall, the findings demonstrate that the
decoction may mediate its reported antihepatocarcinogenic effect, at
least in part, through the modulating activities of genes involved in
tumour suppression and cell cycle arrest
