Search

Lapachol (LAP) is a natural compound with various biological properties, including anticancer activity. However, its clinical application is limited due to the low aqueous solubility and potential adverse side effects. Nanoemulsions are drug delivery systems that can assist in the administration of hydrophobic drugs, increasing their bioavailability and protecting from degradation. Thus, this study aimed to prepare a LAP-loaded nanoemulsion (NE-LAP), and evaluate its antitumor activity. For this purpose, the nanoemulsion was prepared using a hot homogenization method and characterized morphologically by cryogenic transmission electron microscopy (cryo-TEM). Mean diameter, polydispersity index, and zeta potential was evaluated by DLS, encapsulation efficiency was measured by HPLC. Moreover, the short-term storage stability, the drug release and hemolysis in vitro was determined. Additionally, pharmacokinetic, toxicology and toxicity properties of 99m Tc-NE-LAP were evaluated in a breast cancer (4T1) tumor model. The cryo-TEM showed spherical globules, and the physicochemical characterization of NE-LAP showed a homogeneous stable nanoemulsion with a mean diameter of ∼170 nm, zeta potential of around -20 mV, and encapsulation greater than 85 %. In vitro studies validated that encapsulation did not impair the cytotoxicity activity of LAP. The nanoemulsion was successfully radiolabeled and 99m Tc-NE-LAP showed prolonged blood circulation and tumor affinity was confirmed by tumor-to-muscle ratio. Moreover, NE-LAP showed higher antitumor activity than the free drug and the treatment did not result in any signs of toxicity. Therefore, these findings suggest that NE-LAP can be considered an effective strategy for cancer treatment., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Rhinacanthus nasutus has traditionally been used in the treatment of various disorders including diabetes mellitus. Rhinacanthins-rich extract (RRE) is a semipurified R. nasutus leaf extract that contains 60% w/w of rhinacanthin-C (RC) obtained by a green extraction process. The purpose of this study was to investigate the anti-hyperglycemic and anti-hyperlipidemic activity of RRE (15 mg/kg equivalent to RC content) in comparison to its marker compound RC (15 mg/kg) and the standard drug glibenclamide (Glb) (600 μg/kg) in nicotinamide-streptozotocin induced diabetic rats for 28 days. In addition, the in silico pharmacokinetic and toxicity analysis of RC was also performed. RRE, RC and Glb significantly reduced the FBG, HbA1c and food/water intake while increasing the insulin level and body weight in diabetic rats without affecting the normal rats. The serum lipid, liver and kidney biomarkers were markedly normalized by RRE, RC and Glb in diabetic rats without affecting the normal rats. Moreover, the histopathology of the pancreas revealed that RRE, RC and Glb evidently restored the islets of Langerhans in diabetic rats. The overall results indicated that RRE has equivalent antidiabetic potential to that of RC. Moreover, the in silico pharmacokinetic and toxicity analysis predicts that RC is orally non-toxic, non-carcinogenic and non-mutagenic with a decent bioavailability. The undertaken study suggests that RRE could be used as an effective natural remedy in the treatment of diabetes., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

New therapeutic strategies against leishmaniasis are desirable, since the treatment against disease presents problems, such as the toxicity, high cost and/or parasite resistance. As consequence, new antileishmanial compounds are necessary to be identified, as presenting high activity against Leishmania parasites, but low toxicity in mammalian hosts. Flau-A is a naphthoquinone derivative recently showed to presents an in vitro effective action against Leishmania amazonensis and L. infantum species. In the present work, the in vivo efficacy of Flau-A, which was incorporated into a Poloxamer 407-based micelle system, was evaluated in a murine model against L. amazonensis infection. Amphotericin B (AmB) and Ambisome ® were used as controls. The animals were infected and later treated with the compounds. Thirty days after the treatment, parasitological and immunological parameters were evaluated. Results showed that AmB, Ambisome ® , Flau-A or Flau-A/M-treated animals presented significantly lower average lesion diameter and parasite burden in tissue and organs evaluated, when compared to the control (saline and micelle) groups. Flau-A or Flau-A/M-treated mice were those presenting the most significant reductions in the parasite burden, when compared to the others. These animals developed also a more polarized antileishmanial Th1 immune response, which was based on significantly higher levels of IFN-γ, IL-12, TNF-α, GM-CSF, and parasite-specific IgG2a isotype; associated with low levels of IL-4, IL-10, and IgG1 antibody. The absence of toxicity was found in these animals, although mice receiving AmB have showed high levels of renal and hepatic damage markers. In conclusion, results suggested that the Flau-A/M compound may be considered as a possible therapeutic target to be evaluated against human leishmaniasis., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Numerous naphthoquinone derivatives, such as rhinacanthins function as anticancer drugs, which target hTopoII. The structure of hTopoII contains both an ATPase domain and a DNA binding domain. Several drugs bind to either one or both of these domains, thus modifying the activity of hTopoII. The naphthoquinone esters and amides used in this study showed that their hTopoIIα inhibitory activity was inversely proportional to ATP concentration. In order to better characterize the inhibitory action of these compounds, sufficient quantities of soluble functional hTopoII-ATPase domain were required. Therefore, both the alpha and beta isoforms of the hTopoII-ATPase domain were over-expressed in Escherichia coli. The hTopoIIα-ATPase activity was reduced in the presence of naphthoquinone derivatives. Additionally, a molecular docking study revealed that the selected naphthoquinone ester and amide bind to the ATP-binding domain of hTopoIIα. Collectively, the results here provide for the first time a novel insight into the interaction between naphthoquinone esters and amides, and the ATP-binding domain of hTopoIIα. The further elucidation of the mechanism of action of the naphthoquinone esters and amides inhibitory activity is essential., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Dioncoquinones belong to a family of natural naphthoquinone products of interest due to their promising anti-tumoral and anti-infective activities. In particular, dioncoquinones A (5) and B (6) have been shown to be highly active against Leishmania major and multiple myeloma cells without any significant toxicity toward normal blood cells. Their effective concentrations against multiple myeloma cell lines were similar to those of melphalan, a well known DNA-alkylating agent used in a standard therapy against B cell lymphoma and multiple myeloma. We report on the first total synthesis of the highly oxygenated anti-tumoral agent dioncoquinone B (6) and the isolation of its new, even higher-oxygenated analogs, dioncoquinones C (7), D (8), and E (9), from cell cultures of Triphyophyllum peltatum. In addition, several derivatives of these compounds were synthesized, including dioncoquinone C (7), and a small library of naphthoquinones was created. Furthermore, the first structure-activity relationship (SAR) study on this class of compounds was conducted, showing that each of the three hydroxy groups, at C-3, C-5, and C-6, is required for improved anti-tumoral activities and decreased cytotoxicities., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)