Integrative natural medicine inspired graphene nanovehicle-benzoxazine derivatives as potent therapy for cancer.
TL;DR: Interestingly, the benzoxazine derivatives of eugenol with GO nanoparticle exhibited enhanced therapeutic potential in cancer cells and significant role of these derivatives on parasite suggesting its multi-pharmacological capability.
Abstract: Natural products from medicinal plants have always attracted a lot of attention due to their diverse and interesting therapeutic properties. We have employed the principles of green chemistry involving isomerization, coupling and condensation reaction to synthesize a class of compounds derived from eugenol, a naturally occurring bioactive phytophenol. The compounds were characterized structurally by 1H-, 13C-NMR, FT-IR spectroscopy and mass spectrometry analysis. The purity of compounds was detected by HPLC. The synthesized compounds exhibited anti-cancer activity. A 10–12-fold enhancement in efficiency of drug molecules (~ 1 µM) was observed when delivered with graphene oxide (GO) as a nanovehicle. Our data suggest cell death via apoptosis in a dose-dependent manner due to increase in calcium levels in specific cancer cell lines. Interestingly, the benzoxazine derivatives of eugenol with GO nanoparticle exhibited enhanced therapeutic potential in cancer cells. In addition to anti-cancer effect, we also observed significant role of these derivatives on parasite suggesting its multi-pharmacological capability.
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TL;DR: Nanographene has emerged as the material of the century in materialize fields of 'Chemical' fields as mentioned in this paper, and has achieved significant authentication and has been used in many applications.
Abstract: Smart electronic materials ‘nanographene’ stated, its significant authentication has undergone massive improvements and has emerged as a ‘material of the century’ in materialize fields of ‘Chemical...
54 citations
TL;DR: It is shown that ionic imbalance caused by scaffold 7 induces autophagy that leads to onset of apoptosis in the parasite evident by the loss of mitochondrial membrane potential (ΔΨm) and DNA degradation.
Abstract: Natural products offer an abundant source of diverse novel scaffolds that inspires development of next generation anti-malarials. With this vision, a library of scaffolds inspired by natural biologically active alkaloids was synthesized from chiral bicyclic lactams with steps/scaffold ratio of 1.7:1. On evaluation of library of scaffolds for their growth inhibitory effect against malaria parasite we found one scaffold with IC50 in low micro molar range. It inhibited parasite growth via disruption of Na+ homeostasis. P-type ATPase, PfATP4 is responsible for maintaining parasite Na+ homeostasis and is a good target for anti-malarials. Molecular docking with our scaffold showed that it fits well in the binding pocket of PfATP4. Moreover, inhibition of Na+-dependent ATPase activity by our potent scaffold suggests that it targets parasite by inhibiting PfATP4, leading to ionic imbalance. However how ionic imbalance attributes to parasite's death is unclear. We show that ionic imbalance caused by scaffold 7 induces autophagy that leads to onset of apoptosis in the parasite evident by the loss of mitochondrial membrane potential (ΔΨm) and DNA degradation. Our study provides a novel strategy for drug discovery and an insight into the molecular mechanism of ionic imbalance mediated death in malaria parasite.
18 citations
TL;DR: The present article reviews the latest developments in the methodologies of synthesis, pharmacological properties, and further applications of eugenol derivatives.
Abstract: Eugenol (4-allyl-2-methoxyphenol) is a volatile phenolic bioactive compound derived from a natural resource. This compound has been identified in several aromatic plants, among which Syzygium aromaticum (L.) Merr. and L.M. Perry contains between 45 and 90% of eugenol in its essential oil compared to other natural sources. Eugenol has been studied over the years and has shown to display a wide range of biological activities as antifungal, antimicrobial, anti-inflammatory, antioxidant, analgesic, anticancer, and antiparasitic. It has been extensively used in cosmetics, in food processing industry, and also as a starting material for total synthesis of several natural products. The 4-allyl-2-methoxyphenol has a simple structure, which presents three active sites: hydroxyl, allylic, and aromatic groups. Thus, the chemistry of this natural component emphasizes its potential impact in the synthesis of novel drugs, compounds that can be useful for human resources. Therefore, the present article reviews the latest developments in the methodologies of synthesis, pharmacological properties, and further applications of eugenol derivatives.
17 citations
TL;DR: EMD was identified as a novel potent compound targeting oncogenic c-Myc that may offer new opportunities for lung cancer treatment and support its use in potential new approaches to treat c- myc–driven cancer.
Abstract: Aberrant c-Myc is a common feature in the majority of human cancers and has been linked to oncogenic malignancies. As a profound activator of aggressive lung cancer, targeting c-Myc would lead to the better clinical outcome. Here we develop a novel c-Myc targeted compound N, N-bis (5-ethyl-2-hydroxybenzyl) methylamine (EMD) and present evidence demonstrating its effectiveness in targeting c-Myc for degradation in human lung carcinoma. EMD exhibited strong cytotoxicity towards various human lung cancer cell lines ae well as chemotherapeutic-resistant patient-derived lung cancer cells through apoptosis induction, in comparison to chemotherapeutic drugs. Mechanistically, EMD eliminates c-Myc in the cells and initiates caspase-dependent apoptosis cascade. Cycloheximide chase assay revealed that EMD significantly shortened c-Myc half-life by approximately two-fold. Cotreatment of EMD with proteasome inhibitor MG132 reversed its c-Myc targeting effect, suggesting the involvement of ubiquitin-mediated proteasomal degradation in the process. We further verified that EMD strongly induced the ubiquitination of c-Myc that prompted it for protein degradation. c-Myc inhibition and apoptosis induction were additionally shown in hematologic malignant K562, indicating the generality of the observed EMD effects. Altogether, we have identified EMD as a novel potent compound targeting oncogenic c-Myc, which may offer new opportunities for lung cancer treatment. SIGNIFICANCE STATEMENT Deregulation of c-Myc is frequently associated with cancer progression. This study examined the effect of a new compound EMD in targeting c-Myc in several lung cancer cell lines and drug-resistant primary lung cancer cells. EMD induced dramatic c-Myc degradation through ubiquitin-proteasomal mechanism. The promising anti-cancer and c-Myc targeted activities of EMD support its potential new approaches to treat c-Myc driven cancer.
11 citations
Cites background from "Integrative natural medicine inspir..."
...The identified chemical derivative structures have previously been shown to trigger apoptotic cell death in various cancer cell types (Kumar et al., 2019), yet their function to target c-Myc has never been explored....
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...As this is a newly synthesized compound, data on this compound are limited, although a previous study showed that benzoxazine derivatives could induce apoptosis in various cancerous cell types, such as breast cancer, cervical cancer, and osteosarcoma (Kumar et al., 2019)....
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TL;DR: In this paper, a series of 2,4-aryl-4-((arylsulfonyl)methyl)-4H-benzo[d][1,3]oxazines were obtained from N-(2-vinylphenyl)amides and thiols by employing a mixture of K2S2O8-activated charcoal in aqueous acetonitrile solution at 50 °C.
Abstract: A series of 2,4-aryl-4-((arylsulfonyl)methyl)-4H-benzo[d][1,3]oxazines in good to excellent yields have directly been obtained from N-(2-vinylphenyl)amides and thiols by employing a mixture of K2S2O8-activated charcoal in aqueous acetonitrile solution at 50 °C. A plausible mechanism for the reaction is reported. It reveals that the reaction follows a radical pathway and the persulfate has been the oxygen source for formation of the sulfone group in the products. It is worth mentioning that this protocol utilizes an easily accessible K2S2O8-activated charcoal mixture and thiols, respectively, as an oxidant and sulfonylating precursors for the first time.
8 citations
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TL;DR: A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation and is used to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
50,114 citations
TL;DR: An improved method for the preparation of graphene oxide (GO) is described, finding that excluding the NaNO(3), increasing the amount of KMnO(4), and performing the reaction in a 9:1 mixture of H(2)SO(4)/H(3)PO(4) improves the efficiency of the oxidation process.
Abstract: An improved method for the preparation of graphene oxide (GO) is described. Currently, Hummers’ method (KMnO4, NaNO3, H2SO4) is the most common method used for preparing graphene oxide. We have found that excluding the NaNO3, increasing the amount of KMnO4, and performing the reaction in a 9:1 mixture of H2SO4/H3PO4 improves the efficiency of the oxidation process. This improved method provides a greater amount of hydrophilic oxidized graphene material as compared to Hummers’ method or Hummers’ method with additional KMnO4. Moreover, even though the GO produced by our method is more oxidized than that prepared by Hummers’ method, when both are reduced in the same chamber with hydrazine, chemically converted graphene (CCG) produced from this new method is equivalent in its electrical conductivity. In contrast to Hummers’ method, the new method does not generate toxic gas and the temperature is easily controlled. This improved synthesis of GO may be important for large-scale production of GO as well as the ...
9,812 citations
TL;DR: Up-to-date estimates of the cancer burden in Europe alongside the description of the varying distribution of common cancers at both the regional and country level provide a basis for establishing priorities to cancer control actions in Europe.
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TL;DR: The dual role of Ca2+ in living organisms is discussed in this paper, where it has been shown that cellular Ca 2+ overload, or perturbation of intracellular Ca2 + compartmentalization, can cause cytotoxicity and trigger either apoptotic or necrotic cell death.
Abstract: To live or to die? This crucial question eloquently reflects the dual role of Ca2+ in living organisms--survival factor or ruthless killer. It has long been known that Ca2+ signals govern a host of vital cell functions and so are necessary for cell survival. However, more recently it has become clear that cellular Ca2+ overload, or perturbation of intracellular Ca2+ compartmentalization, can cause cytotoxicity and trigger either apoptotic or necrotic cell death.
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TL;DR: The results indicate that the phase in apoptosis that is characterized by chromatin condensation coincides with phosphatidylserine exposure, which precedes membrane damage that might lead to release from the cells of enzymes that are harmful to the surrounding tissues.
2,465 citations