ABSTRACT
We report the synthesis of 47 new quinone-based derivatives via click chemistry and their subsequent evaluation against cancer cell lines and the control L929 murine fibroblast cell line. These compounds combine two redox centers, such as an ortho-quinone/para-quinone or quinones/selenium with the 1,2,3-triazole nucleus. Several of these compounds present IC50 values below 0.5 µM in cancer cell lines with significantly lower cytotoxicity in the control cell line L929 and good selectivity index. Hence, our study confirms the use of a complete and very diverse range of quinone compounds with potential application against certain cancer cell lines.
ABSTRACT
In continuation of our quest for new redox-modulating catalytic antitumor molecules, selenium-containing quinone-based 1,2,3-triazoles were synthesized using rhodium-catalyzed C-H bond activation and click reactions. All compounds were evaluated against five types of cancer cell lines: HL-60 (human promyelocytic leukemia cells), HCT-116 (human colon carcinoma cells), SF295 (human glioblastoma cells), NCIH-460 (human lung cells) and PC3 (human prostate cancer cells). Some compounds showed good activity with IC50 values below 1 µM. The cytotoxic potential of the naphthoquinoidal derivatives was also evaluated in non-tumor cells, exemplified by L929 cells. Overall, these compounds represent promising new lead derivatives and stand for a new class of chalcogenium-containing derivatives with potential antitumor activity.
Subject(s)
Antineoplastic Agents/chemical synthesis , Organoselenium Compounds/chemical synthesis , Quinones/chemistry , Rhodium/chemistry , Triazoles/chemical synthesis , Antineoplastic Agents/therapeutic use , Catalysis , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Click Chemistry , Drug Screening Assays, Antitumor , Humans , Organoselenium Compounds/pharmacology , Structure-Activity Relationship , Triazoles/pharmacologyABSTRACT
The objective of this study was to evaluate the antiproliferative, cytotoxic and genotoxic potential of salty liquid synthetic flavorings of Butter, Cheddar Cheese and Onion. The antiproliferative potential (2.9-1500 µg/mL) was assessed by MTT assay after 72h using the human tumor lines SF-295 (glioblastoma), OVCAR-8 (ovarian), HCT-116 (colon) and HL-60 (promyelocytic leukemia) and primary cultures of murine Sarcoma 180 (S180) and peripheral blood mononuclear cells (PBMC). Allium cepa bulbs were exposed to growing respective doses (1 mL and 2 mL). Only Butter and Cheddar flavorings revealed cytotoxic activity on cancer cells, with IC50 values ranging from 125.4 µg/mL (Cheddar - HCT-116) to 402.6 µg/mL (Butter - OVCAR-8). Butter flavoring was the most cytotoxic on PBMC (136.3 µg/mL) and increased cell division rate in relation to the mitotic index but did not cause cellular aberrations. Onion and Cheddar flavorings reduced the mitotic index after 24h and 48h exposure, but only Onion flavoring resulted in cellular aberrations and mitotic spindle abnormalities, such as anaphase and telophase bridges, micronucleated cells, conchicine-metaphases and amplifications. So, Butter, Onion and/or Cheddar flavorings caused significant changes in the division of meristematic cells of A. cepa and presented cytotoxic action even on decontrolled proliferating human tumor cells.
Subject(s)
Antineoplastic Agents/pharmacology , Butter , Cheese , Flavoring Agents/pharmacology , Leukocytes, Mononuclear/drug effects , Onions , Animals , Cell Line, Tumor , Cytotoxins/pharmacology , Formazans , Humans , Meristem/drug effects , Mice , Mitosis/drug effects , Mitotic Index , Mutagens/pharmacology , Onions/drug effects , Tetrazolium SaltsABSTRACT
Pterocarpanquinones (1a-e) and the aza-pterocarpanquinone (2) were synthesized through palladium catalyzed oxyarylation and azaarylation of conjugate olefins, and showed antineoplasic effect on leukemic cell lines (K562 and HL-60) as well as colon cancer (HCT-8), gliobastoma (SF-295) and melanoma (MDA-MB435) cell lines. Some derivatives were prepared (3-8) and evaluated, allowing establishing the structural requirements for the antineoplasic activity in each series. Compound 1a showed the best selectivity index in special for leukemic cells while 2 showed to be more bioselective for HCT-8, SF-295 and MDA-MB435 cells. Pterocarpanquinones 1a and 1c-e, as well as 8 were the most active on amastigote form of Leishmania amazonensis in culture. Compounds 1a, 1c and 8 showed the best selectivity index.
Subject(s)
Antineoplastic Agents/chemistry , Leishmania mexicana/drug effects , Pterocarpans/chemistry , Quinones/chemistry , Trypanocidal Agents/chemistry , Animals , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , K562 Cells , Mice , Mice, Inbred BALB C , Pterocarpans/chemical synthesis , Pterocarpans/pharmacology , Quinones/chemical synthesis , Quinones/pharmacology , Structure-Activity Relationship , Trypanocidal Agents/pharmacologyABSTRACT
Four derivatives of an α,ß-amyrin mixture were synthesized by acylation with appropriate anhydrides. The structures of the compounds were confirmed by means of IR and (1)H and (13)C NMR. The compounds were screened for cytotoxic activity using four human tumor cell lines (HL-60, MDAMB-435, SF-295 and HCT-8) and normal peripheral blood mononuclear cells (PBMC). 3-O-Carboxymaleinate of α,ß-amyrin (3a/3b) were found to be the only active compounds of the series (high cytotoxicity), showing IC(50) values ranging from 1.8 to 3µM. In PBMC, 3a/3b were not toxic, suggesting selectivity for tumor cells. To better understand the mechanism of action involved in the cytotoxicity of 3a/3b, HL-60 cells treated with 3a/3b were examined for morphological changes, DNA fragmentation, cell cycle perturbation, externalization of phosphatidylserine and activation of caspases 3/7, with doxorubicin serving as the positive control. The results indicate that the cytotoxicity of 3a/3b involves the induction of cell death by apoptosis.
