Synthetically modified methoxsalen for enhanced cytotoxicity in light and dark reactions.

Published on Feb 15, 2019in Bioorganic & Medicinal Chemistry Letters2.572
· DOI :10.1016/J.BMCL.2018.12.048
Christophe Guillon8
Estimated H-index: 8
(Lehigh University),
Yi-Hua Jan8
Estimated H-index: 8
(RU: Rutgers University)
+ 4 AuthorsNed D. Heindel20
Estimated H-index: 20
(Lehigh University)
Abstract Linear furocoumarins, also known as psoralens, are clinically useful photo-activated pharmaceuticals employed to address hyperproliferative skin diseases. Seven diverse cytotoxic pharmacophores have been synthetically attached to 8-methoxypsoralen via a 5-amino functionality. The resulting unique set of compounds was evaluated for dark and light toxicity against PAM212 keratinocytes in culture.
#1Paul T. Wilder (UMB: University of Maryland, Baltimore)H-Index: 22
#2David J. Weber (UMB: University of Maryland, Baltimore)H-Index: 51
Last. Santosh K. Mandal (MSU: Morgan State University)H-Index: 8
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Cisplatin and other metal-based drugs often display side effects and tumor resistance after prolonged use. Because rhenium-based anticancer complexes are often less toxic, a novel series of organorhenium complexes were synthesized of the types: XRe(CO)3Z (X = α-diimines and Z = p-toluenesulfonate, 1-naphthalenesulfonate, 2-naphthalenesulfonate, picolinate, nicotinate, aspirinate, naproxenate, flufenamate, ibuprofenate, mefenamate, tolfenamate, N-acetyl-tryptophanate), and their biological proper...
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#1Jeffrey D. Laskin (RU: Rutgers University)H-Index: 69
#2Yi-Hua Jan (RU: Rutgers University)H-Index: 8
Last. Ned D. Heindel (Lehigh University)H-Index: 20
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: Photosensitizers are used in the treatment of epidermal proliferation and differentiation disorders such as psoriasis and vitiligo. In these studies, a ring-expanded carbon homolog of the linear psoralen (furo[3,2-g]benzopyran-7-one) class of photosensitizers, 4,10-dimethyl-2H,8H-benzo[1,2-b:5,4-b']dipyran-2-one (NDH2476), was synthesized and analyzed for biological activity. Following activation by ultraviolet light (UVA, 320-400 nm), NDH2476 was found to be a potent inhibitor of keratinocyte...
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#1Peter G Hains (Children's Medical Research Institute)H-Index: 17
#2Phillip J. Robinson (Children's Medical Research Institute)H-Index: 67
Iodoacetamide is by far the most commonly used agent for alkylation of cysteine during sample preparation for proteomics. An alternative, 2-chloroacetamide, has recently been suggested to reduce the alkylation of residues other than cysteine, such as the N-terminus, Asp, Glu, Lys, Ser, Thr, and Tyr. Here we show that although 2-chloroacetamide reduces the level of off-target alkylation, it exhibits a range of adverse effects. The most significant of these is methionine oxidation, which increases...
19 CitationsSource
#1Justin A. Pals (UIUC: University of Illinois at Urbana–Champaign)H-Index: 7
#2Elizabeth D. Wagner (UIUC: University of Illinois at Urbana–Champaign)H-Index: 40
Last. Matias S. Attene-Ramos (GW: George Washington University)H-Index: 1
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Abstract Haloacetamides (HAMs) are cytotoxic, genotoxic, and mutagenic byproducts of drinking water disinfection. They are soft electrophilic compounds that form covalent bonds with the free thiol/thiolate in cysteine residues through an S N 2 reaction mechanism. Toxicity of the monohalogenated HAMs (iodoacetamide, IAM; bromoacetamide, BAM; or chloroacetamide, CAM) varied depending on the halogen substituent. The aim of this research was to investigate how the halogen atom affects the reactivity...
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#1Dorota Wrześniok (University of Silesia in Katowice)H-Index: 17
#2Artur Beberok (University of Silesia in Katowice)H-Index: 13
Last. Ewa Buszman (University of Silesia in Katowice)H-Index: 19
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AbstractPurpose: Melanoma is an aggressive form of skin cancer. The aim of the study was to evaluate the influence of UVA radiation and psoralens: 5-methoxypsoralen (5-MOP) or 8-methoxypsoralen (8-MOP) on melanoma cells viability.Materials and methods: The amelanotic C32 and melanotic COLO829 human melanoma cell lines were exposed to increasing concentrations of psoralens (0.1–100 μM) in the presence or absence of UVA radiation. Cell viability was evaluated by the WST-1 assay.Results: We demonst...
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#1Jovana Francuz (University of Novi Sad)H-Index: 11
#2Ivana Kovačević (University of Novi Sad)H-Index: 7
Last. Velimir Popsavin (University of Novi Sad)H-Index: 16
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Abstract A series of new antitumour lactones containing the [3.3.0] bicyclic furano-lactone core and the halogen or azido group at the C-7 position have been designed, synthesized, and evaluated for their in vitro antitumour activity against a panel of human tumour cell lines. Some of the analogues displayed powerful antiproliferative effects to certain human tumour cells, but all of them were devoid of any cytotoxicity towards the normal foetal lung fibroblasts (MRC-5). A SAR study reveals the ...
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#1Chunhua Yang (Xuzhou Medical College)H-Index: 1
#1Chunhua Yang (Xuzhou Medical College)H-Index: 2
Last. Li-jun MaoH-Index: 3
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Conditionally replicating adenoviruses have emerged as novel therapeutic agents for cancer. This study aimed to evaluate synergistic antitumor activity of replication-competent adenovirus armed with interleukin (IL)-18 (ZD55-IL-18) and dacarbazine (DTIC) against melanoma. Melanoma A375 cells or nude mouse tumor xenografts were treated with ZD55-IL-18 alone or together with DTIC. The results showed that ZD55-IL-18 competently replicated in A375 cells and expressed IL-18, and these were not affect...
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#1Zhiqiang Qin (Nanjing Medical University)H-Index: 27
#2Xiao LiH-Index: 5
Last. Qing ZouH-Index: 6
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AbstractBackground:Recently, increasing relevant studies researched the efficacy of castration resistant prostate cancer (CRPC) patients using chemotherapy with or without estramustine, in order to assess the efficacy and toxicity of combining estramustine with chemotherapy for the treatment of CRPC
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#1Elisa Kinski (FAU: University of Erlangen-Nuremberg)H-Index: 2
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Abstract Aminoferrocene-based prodrugs are activated in the presence of cancer-specific amounts of reactive oxygen species, e.g. H 2 O 2 , with the formation of products of two types: Fe-containing complexes, which catalyze generation of HO and O 2 − , and quinone methides, which alkylate glutathione and inhibit the antioxidative system of the cell. Both processes act synergistically by increasing the oxidative stress in cancer cells thereby leading to their death. However, in the activation ste...
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Last. Jian Yang (Nanjing Medical University)H-Index: 17
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Abstract Despite progress in diagnostics and treatment of hepatocellular carcinoma (HCC), its prognosis remains poor. 8-Methoxypsoralen (8-MOP), a formerly considered photosensitizing agent, has been reported to induce cell apoptosis in HepG2 cells in a modest way when used alone. In this study, it was demonstrated that 8-MOP inhibited HCC HepG2 cells and SMMC-7721 cells migratory and invasive potentiality, as well as modulated the expression of various EMT-associated genes such as enhancing E-c...
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Abstract Infections caused by virus are one of the foremost causes of morbidity and mortality in the world. Although a number of antiviral drugs are currently used for treatment of various kinds of viral infection diseases, there is still no available therapeutic agent for the most of virus in clinical practice. Coumarin is a chemical compound which is found naturally in a variety of plants, as well as it can be synthetically produced possessing diverse biological effects. More recently, reports...
#1Salman Ahmed (KU: University of Karachi)H-Index: 8
#2Haroon Khan (AWKUM: Abdul Wali Khan University Mardan)H-Index: 34
Last. Raffaele Capasso (University of Naples Federico II)H-Index: 57
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Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative op...
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Abstract Zanthoxylum species and volatile oils have shown to have insect resistance. The present work was conducted to find alternative botanical source with significant activity on storage pests control. Chemical examination of Zanthoxylum dimorphophyllum Hemsl. var. spinifolium Rehder et E. H. Wilson stem bark has led to fifteen coumarins, which including two were novel compounds named 6-(2′,3′-dihydroxy-3′-methylbutyl)-7-hydroxyl-8-(3″-methyl-2″-butenyl)-2H-1-benzopyran-2-one (7) and 6-(2′-hy...
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Abstract Multi-target molecular entities, offer a path to progress both in understanding causes of disease and in defining effective small molecule treatments. Coumarin and its derivatives belong to an important group of natural compounds with diverse biological properties. They are found in vegetables and plants for which literature reports thousands of publications for the great variety of biological applications among which the photoprotective effects, thus being considered multi-targeting ag...
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