Original Article. Study of the cytotoxic/toxic potential of the novel anticancer selenodiazoloquinolone on fibroblast cells and 3D skin model (original) (raw)
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Immunological Investigations, 2017
Our previous studies on leukemia cells L1210 and cervical cancer HeLa cells revealed cytotoxic effects of the 7-ethyl 9-ethyl-6-oxo-6,9-dihydro [1,2,5]selenadiazolo[3,4-h]quinoline-7-carboxylate (E2h), a new synthetically prepared quinolone derivative, toward selected cancer cell lines. The aim of the present study was to examine the cytotoxicity of E2h toward next cell lines and tissues; that is, human cancer HL-60 and A549 cells, human non-cancer fibroblast BHNF-1 cells, and reconstructed human epidermis tissues. Further we investigated the immunomodulatory activity of E2h on murine macrophage RAW 264.7 cells. Selenadiazoloquinolone E2h induced specific antiproliferative/cytotoxic activity against leukemia HL-60 cells and is the potent inducer of apoptotic cell death. Quinolone derivative demonstrated the immunomodulatory activities on RAW 264.7 cell line murine macrophages. The immunobiological studies revealed time-and concentration-dependent effective immunomodulation of pro-and anti-inflammatory cytokines' release and antiproliferative/cytotoxic effect following exposure of RAW 264.7 cells to E2h.
2010
The present study demonstrated cytotoxic/phototoxic effects of new synthetically prepared quinolone ethyl-1,4-dihydro-8-nitro-4-oxoquinoline -3-carboxylate (DNQC) on human leukemia cells HL-60. The effects on cell prolifera tion, cell cycle, induction of apoptotic/necrotic cell death and DNA damage in dark and in the presence of UVA irradiation were evaluated. DNQC induced a different cytotoxic/phototoxic effect which was concentration- and time-dependent. UVA irradiation statistically increased DNQC effect on HL-60 cells. The IC 50 and IC 100 values showed that the irradiated HL-60 cells are 5.4 ‐ 27.0 (IC 50 ) and 2.5 ‐ 15.0 (IC 100 ) times more sensitive in comparison to the non-ir radiated cells. The cytotoxic/phototoxic concentrations of DNQC induced necrotic death of leukemia cells HL-60. Dead cells had the integrity damage of cytop lasmic membrane and DNA damage. The DNA damage generated by DNQC alone/with combination of UVA irradiation induced cell cycle changes and led to n...
International Journal of Oncology, 2010
Substituted quinolines (PQ code number), which reduce colony formation and increase gap junctional intercellular communication, were tested for their ability to interact with various molecular targets in murine and human tumor cell lines in vitro. Various markers of tumor cell metabolism, DNA fragmentation, mitotic disruption, apoptosis induction and growth factor receptor signaling pathways were assayed in vitro to evaluate drug cytotoxicity. Based on its ability to inhibit the metabolic activity of suspension cultures of leukemic L1210 cells at days 2 and 4 in vitro, PQ1 succinic acid salt is the most effective antiproliferative agent among the synthetic quinoline analogs tested. Moreover, antiproliferative PQ1 is effective across a spectrum of monolayer cultures of pancreatic Pan02, epidermoid A-431 and mammary SK-BR-3 and BT-474 tumor cells. PQ1 also blocks Ki-67 expression, a marker of tumor cell proliferation. A 1.5-to 3-h treatment with PQ1 is sufficient to inhibit the incorporations of [ 3 H]thymidine into DNA, [ 3 H]-uridine into RNA and [ 3 H]-leucine into protein used to assess the rates of macromolecule syntheses over a 0.5-or 1-h period of pulse-labeling in L1210 tumor cells. A 15-min pretreatment with PQ1 inhibits the cellular transport of both purine and pyrimidine nucleosides over a 30-sec period in vitro, suggesting that PQ1 may prevent the incorporation of [ 3 H]-adenosine and [ 3 H]-thymidine into DNA because it rapidly blocks the uptake of these nucleosides by the tumor cells. Since PQ1 does not reduce the fluorescence of the ethidium bromide-DNA complex, it does not directly bind to or destabilize double-stranded DNA. Over a 6-to-48-h period, PQ1 has very little effect on the mitotic index of L1210 cells but stimulates the formation of many binucleated cells and a few micronuclei, suggesting that this compound might increase mitotic abnormality, induce chromosomal damage or missegregation, and block cytokinesis. The fact that PQ1 induces initiator caspase-2 and effector caspase-3 activities and poly(ADP-ribose) polymerase-1 cleavage within 1-4 h and internucleosomal DNA fragmentation within 24 h in L1210 cells suggests that this antitumor drug can trigger the early and late events required for cells to undergo apotosis. Whole-cell immunodetection and Western blot analysis indicate that, in contrast to 17-(allylamino)-17-demethoxygeldanamycin and radicicol, PQ1 fails to down-regulate the protein level at 24 h and autophosphorylation at 3 h of membrane-anchored HER1 in A-431 cells and HER2 in SK-BR-3 cells, suggesting that this antitumor compound is unlikely to interact with and inhibit Hsp90 and the epidermal growth factor (EGF) receptor signaling pathways. In conclusion, antiproliferative PQ1 is effective against a spectrum of tumor cells and might interact with various membrane and nuclear targets to enhance gap junctions, inhibit nucleoside transport and block cytokinesis but does not appear to disrupt the EGF receptor-mediated signaling pathways to induce growth arrest and apoptosis.
Arabian Journal of Chemistry, 2013
2-Quinolone analogs are powerful inhibitors of farnesyl transferase, and are a novel class of anticancer drugs. The present study focused on continual efforts to elucidate the anticancer activity of synthesized 2-quinolone derivatives without N-methyl or 3-aryl substitution. Three derivatives namely JST, JST2 and JST13 were synthesized in our lab and screened for in vitro and in vivo anticancer activities. Significant cytotoxicity was observed in MCF-7 cells treated with JST2 and JST13. Both the derivatives' treatment showed damage to the DNA. In vivo studies for JST2 and JST13 were performed at two doses 100 and 200 mg/kg using Ehrlich ascites carcinoma (liquid) and Dalton lymphoma ascites (solid) models. Both derivatives showed a significant reduction in the tumor progression by increasing the mean life span and by improving the haematological profile and antioxidant status of the liver in a liquid tumor model. More prominent effect was observed in a solid tumor model by reduction in solid tumor weight and tumor volume.
Molecules
Our previous study found that 2-phenyl-4-quinolone (2-PQ) derivatives are antimitotic agents, and we adopted the drug design concept of scaffold hopping to replace the 2-aromatic ring of 2-PQs with a 4-aromatic ring, representing 4-phenyl-2-quinolones (4-PQs). The 4-PQ compounds, whose structural backbones also mimic analogs of podophyllotoxin (PPT), maybe a new class of anticancer drugs with simplified PPT structures. In addition, 4-PQs are a new generation of anticancer lead compounds as apoptosis stimulators. On the other hand, previous studies showed that 4-arylcoumarin derivatives with 5-, 6-, and 7-methoxy substitutions displayed remarkable anticancer activities. Therefore, we further synthesized a series of 5-, 6-, and 7-methoxy-substituted 4-PQ derivatives (19–32) by Knorr quinoline cyclization, and examined their anticancer effectiveness. Among these 4-PQs, compound 22 demonstrated excellent antiproliferative activities against the COLO205 cell line (50% inhibitory concentr...
Cytotoxic–antineoplastic activity of hydroquinone derivatives
European Journal of Medicinal Chemistry, 2002
Several myrcenylhydroquinone derivatives have been evaluated for their cytotoxic activity against three neoplastic cell line cultures and compared with the activity previously observed on other neoplastic systems. Also a new series of this type of compounds has been prepared and the compounds synthesised have been evaluated by their GI 50 values.
In-vitro Cytotoxicity Assay of Quinoxalines
Journal of Current Pharma Research, 2017
Major objective of work is in-vitro cytotoxicity assay of newly synthesized compounds and estimated deaths due to the cancer in human beings in US. Current manuscript also provides the chemotherapy of cancer with highly active and safe anti-cancer synthesized quinoxaline compounds and their in-vitro assay at National Cancer Institute (NCI). A series of new quinoxaline derivatives 3 (a-h) has been prepared. The newly synthesized compounds were further evaluated in the National Cancer Institute for their in-vitro cytotoxicity assay. Among them compound 3h has been show highest activity against Leukemia RPMI-8226 cell lines (GI 50 : 1.11 μM) as compared to other tested compounds. It is to be noted that compound 3e has been show significant activity against cancer cell lines. (GI 50 : 1.11 μM). We conclude that the ongoing studies of targeted agents in conjunction with chemotherapy will show whether there are alternative option for new and safer medicine for cancer in future as well as opens the new doors in era of cancer research. .
Anticancer Activity of Quinoline Derivatives; An Overview
International Journal of Pharmaceutical Sciences Review and Research
Quinoline, 1-aza naphthalene/benzo pyridine, is nitrogen containing heterocyclic nucleus which is one of the major building blocks of many synthetic drugs. Quinoline derivatives have attracted many scholars’ attention because of their wide range of pharmacological activities such as antimalarial, anticancer, anti-inflammatory, antimicrobial etc. There are so many quinoline derivatives with anticancer activities were reported in various renowned journals. In this review, an attempt is made to compile the latest updates on anticancer activity of quinoline derivatives. Quinoline derivatives plays an important role in anticancer drug development through different mechanism of action like topoisomerase I and II inhibition, proteasome inhibition, antimitotic and tubulin polymerization inhibition etc.
Journal of Medicinal Chemistry, 2013
A series of 7-amino-and 7-acetamidoquinoline-5,8-diones with aryl substituents at the 2-position were synthesized, characterized and evaluated as potential NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor agents. The synthesis of lavendamycin analogs is illustrated. Metabolism studies demonstrated that 7-amino-analogues were generally better substrates for NQO1 than 7-amido-analogues as were compounds with smaller heteroaromatic substituents at the C-2 position. Surprisingly, only two compounds, 7-acetamido-2-(8'-quinolinyl)quinoline-5,8dione (11) and 7-amino-2-(2-pyridinyl)quinoline-5,8-dione (23) showed selective cytotoxicity toward the NQO1-expressing MDA468-NQ16 breast cancer cells versus the NQO1-null MDA468-WT cells. For all other compounds, NQO1 protected against quinoline-5,8-dione cytotoxicity. Compound 22 showed a potent activity against human breast cancer cells expressing or not expressing NQO1 with IC50 values of respectively 190 nM and 140 nM and a low NQO1 mediated reduction rate, which suggests that the mode of action of 22 differs from lavendamycin and involves an unidentified target(s).
Immunobiology, 2018
The present study examined the cytotoxicity, anti-cancer reactivity, and immunomodulatory properties of new synthetically prepared fluoroquinolone derivative 6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate (6FN) in vitro. The cytotoxicity/toxicity studies (concentrations in the range 1-100 μM) are focused on the cervical cancer cells HeLa, murine melanoma cancer cells B16, non-cancer fibroblast NIH-3T3 cells and reconstructed human epidermis tissues EpiDerm™. The significant growth inhibition of cancer cells HeLa and B16 was detected. The cytotoxicity was mediated via apoptosis-associated with activation of caspase-9 and-3. After 72 h of treatment, the two highest 6FN concentrations (100 and 50 μM) induced toxic effect on epidermis tissue EpiDerm™, even the structural changes in tissue were observed with concentration of 100 μM. The effective induction of RAW 264.7 macrophages cell-release of pro-and anti-inflammatory T H 1, T H 2 and T H 17 cytokines, with anti-cancer and/or anti-infection activities, respectively, has been revealed even following low-dose exposition.