Synthesis and evaluation of the cytotoxic activity of 1,2-furanonaphthoquinones tethered to 1,2,3-1H-triazoles in myeloid and lymphoid leukemia cell lines

Cardoso, Mariana F. C.; Rodrigues, Patrícia Corrêa; Oliveira, Maria Auxiliadora; Gama, Ivson Lelis; Silva, Illana M. C. B. da; Santos, Isabela O.; Rocha, David R. da; Pinho, Rosa Teixeira de; Ferreira, Vı́tor F.; Souza, Maria Cecília B. V. de; Silva, Fernando de Carvalho da; Silva, Floriano Paes

doi:10.1016/j.ejmech.2014.07.079

Cited by 43 publications

(20 citation statements)

References 57 publications

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“…Compounds 25a and 25b were synthesized by Cardoso et al in 2014 [108] as part of a series of 1,2-furanonaphthoquinones linked to 1,2,3-1 H -triazoles with the objective of investigating their antileukemic activity in lymphoid (MOLT-4 and CEM) and myeloid (K562 and KG1) leukemia cell lines The former has good potential for further studies since it turned out to be a potent and selective hit towards cancer cell lines also showing preference against leukemia lymphoid cell lines. Compound 25b is also a promising hit with high potency as a cytotoxic agent (IC 50 for leukemia cell lines range between 0.05 and 11.07 µM).…”

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confidence: 99%

The diverse mechanisms and anticancer potential of naphthoquinones

et al. 2019

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Cancer is one of the leading causes of death around the world and although the different clinical approaches have helped to increase survival rates, incidence is still high and so its mortality. Chemotherapy is the only approach which is systemic, reaching cancer cells in all body tissues and the search for new potent and selective drugs is still an attractive field within cancer research. Naphthoquinones, natural and synthetic, have garnered much attention in the scientific community due to their pharmacological properties, among them anticancer action, and potential therapeutic significance. Many mechanisms of action have been reported which also depend on structural differences among them. Here, we describe some of the most relevant mechanisms of action reported so far for naphthoquinones and highlight novel targets which are being described in the literature. Furthermore, we gather some of the most impressive efforts done by researchers to harness the anticancer properties of these compounds through specifically designed structural modifications.

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Section: Main Textmentioning

confidence: 99%

The diverse mechanisms and anticancer potential of naphthoquinones

et al. 2019

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“…Multi-substituted naphthoquinones, including shikonin [35,36,37,38,39] and its derivative SH-7 [40], and other dihydroxy or dimethoxy 1,4-naphthoquinones [41,42], compared with mono- or di-substituted naphthoquinones, demonstrated superior in vitro activity against AML cells with IC 50 s ranging 0.1–4 μM. Heterocyclic monomeric naphthoquinones included furanonaphthoquinones FNQ3 [43] and FN6-one [44], β-lapachone [45,46,47,48,49] and nor-β-lapachone [45,46,50,51], dunnione [47], and pterocarpanquinone LQB-118 [28,52]. FNQ3 was significantly more effective than low dose cytarabine in reducing cell viability ( p < 0.001) and combining the two drugs led to an even greater reduction in cell viability in NB4 and U937 cells ( p < 0.01) [43].…”

Section: Resultsmentioning

confidence: 99%

Analysis of the Mechanisms of Action of Naphthoquinone-Based Anti-Acute Myeloid Leukemia Chemotherapeutics

et al. 2019

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Acute myeloid leukemia (AML) is a neoplastic disorder resulting from clonal proliferation of poorly differentiated immature myeloid cells. Distinct genetic and epigenetic aberrations are key features of AML that account for its variable response to standard therapy. Irrespective of their oncogenic mutations, AML cells produce elevated levels of reactive oxygen species (ROS). They also alter expression and activity of antioxidant enzymes to promote cell proliferation and survival. Subsequently, selective targeting of redox homeostasis in a molecularly heterogeneous disease, such as AML, has been an appealing approach in the development of novel anti-leukemic chemotherapeutics. Naphthoquinones are able to undergo redox cycling and generate ROS in cancer cells, which have made them excellent candidates for testing against AML cells. In addition to inducing oxidative imbalance in AML cells, depending on their structure, naphthoquinones negatively affect other cellular apparatus causing neoplastic cell death. Here we provide an overview of the anti-AML activities of naphthoquinone derivatives, as well as analysis of their mechanism of action, including induction of reduction-oxidation imbalance, alteration in mitochondrial transmembrane potential, Bcl-2 modulation, initiation of DNA damage, and modulation of MAPK and STAT3 activity, alterations in the unfolded protein response and translocation of FOX-related transcription factors to the nucleus.

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“…(http://www.molin spira tion.com/) online tool kit and OSIRIS property explorer was used for computing drug like characteristics from 2D chemical structures of aforementioned compounds [51][52][53][54]. Pre-ADMET online server (https ://pread met.bmdrc .kr/) was used for calculating pharmacokinetic parameters like adsorption, distribution, metabolism and excretion and some of the computed properties are human intestinal absorption (HIA %), Caco-2 cell permeability (nm/s), MDCK (Medin-Darbey Canine Kidney Epithelial Cells) cell permeability (nm/s), plasma protein binding (%)¸ blood brain barrier penetration (C. brain/C.…”

Section: Molinspirationmentioning

confidence: 99%

Synthesis, molecular docking and molecular dynamic simulation studies of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives as antidiabetic agents

et al. 2020

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A series of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives (5a-5v) has been synthesized and confirmed by physicochemical(R f , melting point) and spectral means (IR, 1 HNMR, 13 CNMR). The results of in vitro antidiabetic study against α-glucosidase indicated that compound 5o bearing 2-CH 3-5-NO 2 substituent on phenyl ring was found to be the most active compound against both enzymes. The electron donating (CH 3) group and electron withdrawing (NO 2) group on a phenyl ring highly favoured the inhibitory activity against these enzymes. The docking simulations study revealed that these synthesized compounds displayed hydrogen bonding, electrostatic and hydrophobic interactions with active site residues. The structure activity relationship studies of these compounds were also corroborated with the help of molecular modeling studies. Molecular dynamic simulations have been done for top most active compound for validating its α-glucosidase and α-amylase inhibitory potential, RMSD analysis of ligand protein complex suggested the stability of top most active compound 5o in binding site of target proteins. In silico ADMET results showed that synthesized compounds were found to have negligible toxicity, good solubility and absorption profile as the synthesized compounds fulfilled Lipinski's rule of 5 and Veber's rule.

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Synthesis and evaluation of the cytotoxic activity of 1,2-furanonaphthoquinones tethered to 1,2,3-1H-triazoles in myeloid and lymphoid leukemia cell lines

Cited by 43 publications

References 57 publications

The diverse mechanisms and anticancer potential of naphthoquinones

The diverse mechanisms and anticancer potential of naphthoquinones

Analysis of the Mechanisms of Action of Naphthoquinone-Based Anti-Acute Myeloid Leukemia Chemotherapeutics

Synthesis, molecular docking and molecular dynamic simulation studies of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives as antidiabetic agents

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