Novel Proline Transporter Inhibitor (LQFM215) Presents Antipsychotic Effect in Ketamine Model of Schizophrenia.

The glutamatergic hypothesis of schizophrenia suggests a correlation between NMDA receptor hypofunction and negative psychotic symptoms. It has been observed that the expression of the proline transporter (PROT) in the central nervous system (CNS) is associated with glutamatergic neurotransmission, as L-proline has the capacity to activate and modulate AMPA and NMDA receptors. In this study, we aimed to investigate whether inhibition of proline transporters could enhance glutamatergic neurotransmission and potentially exhibit antipsychotic effects in an experimental schizophrenia model.

Acute toxicity and antitumor potential of 1,3,4-trisubstituted-1,2,3-triazole dhmtAc-loaded liposomes on a triple-negative breast cancer model.

For the first time, compounds developed from the 1,2,3-triazole scaffold were evaluated as novel drugs to treat triple-negative breast cancer (TNBC). Four organic salts were idealized as nonclassical bioisosteres of miltefosine, which is used in the topical treatment for skin metastasizing breast carcinoma. Among them, derivative dhmtAc displayed better solubility and higher cytotoxicity against the human breast adenocarcinoma cell line and mouse 4T1 cell lines, which are representatives of TNBC.

Evaluation of Toxicity and Oxidative Stress of 2-Acetylpyridine-(4)-orthochlorophenyl Thiosemicarbazone.

Thiosemicarbazones are well known for their broad spectrum of action, including antitumoral and antiparasitic activities. Thiosemicarbazones work as chelating binders, reacting with metal ions. The objective of this work was to investigate the , , and toxicity and oxidative stress of 2-acetylpyridine-(4)-orthochlorophenyl thiosemicarbazone (TSC01).

Morita-Baylis-Hillman adducts derived from thymol: synthesis, in silico studies and biological activity against Giardia lamblia.

Giardiasis is a neglected disease, and there is a need for new molecules with less side effects and better activity against resistant strains. This work describes the evaluation of the giardicidal activity of thymol derivatives produced from the Morita-Baylis-Hillman reaction. Thymol acrylate was reacted with different aromatic aldehydes, using 1,4-diazabicyclo[2.

Shortened derivatives from native antimicrobial peptide LyeTx I: and biological activity assessment.

In the continuing search for novel antibiotics, antimicrobial peptides are promising molecules, due to different mechanisms of action compared to classic antibiotics and to their selectivity for interaction with microorganism cells rather than with mammalian cells. Previously, our research group has isolated the antimicrobial peptide LyeTx I from the venom of the spider . Here, we proposed to synthesize three novel shortened derivatives from LyeTx I (LyeTx I mn; LyeTx I mnΔK; LyeTx I mnΔKAc) and to evaluate their toxicity and biological activity as potential antimicrobial agents.

Evaluation of cobalt(III) complexes as potential hypoxia-responsive carriers of esculetin.

Differentiation between hypoxic and normoxic tissues have been exploited for the development of selective chemotherapeutic agents. In this context, cobalt(III)-based coordination compounds have been designed and investigated as prospective hypoxia-responsive drug delivery systems. Three cobalt(III) complexes, namely [Co(esc)(pyen)]ClO·(CHOH) (1) [Co(esc)(TPA)]ClO·3HO (2) and [Co(bipy)(esc)]ClO·2.

Novel self-nanoemulsifying drug-delivery system enhances antileukemic properties of all- retinoic acid.

All- retinoic acid (ATRA) shows erratic oral bioavailability when administered orally against leukemia, which can be solved through its incorporation in self-nanoemulsifying drug-delivery systems (SEDDS). The SEDDS developed contained a hydrophobic ion pair between benzathine (BZT) and ATRA and was enriched with tocotrienols by the input of a palm oil tocotrienol rich fraction (TRF) in its composition. SEDDS-TRF-ATRA-BZT allowed the formation of emulsions with nanometric size that retained ATRA within their core after dispersion.

Anti-inflammatory and cytotoxic activities of the extracts, fractions, and chemical constituents isolated from Luehea ochrophylla Mart.

Background: Stem bark of Luehea ochrophylla (L. ochrophylla) is used by the traditional Brazilian medicine for treatment of rheumatic diseases and tumors. This study aimed to investigate inhibition of acute and chronic inflammations and cytotoxic activity of extracts, fractions, and isolated compounds from L.

Evaluation of 5-hydroxy-1,4-naphthoquinone-cobalt(III) complexes for hypoxia-activated drug delivery.

Three novel PyNcobalt(III) complexes with the 5-hydroxy-1,4-naphthoquinone nuclei (NQ) were evaluated as potential hypoxia-activated anticancer prodrugs. The complexes were synthesized and fully characterized by IR and UV-Visible spectroscopies, ESI mass spectrometry and CHN elemental analysis. Structural information was obtained from density functional theory (DFT) calculations.

Efficient atrazine degradation catalyzed by manganese porphyrins: Determination of atrazine degradation products and their toxicity evaluation by human blood cells test models.

Atrazine (ATZ) is an herbicide that has been considered an environmental pollutant worldwide. ATZ contaminates groundwaters and can persist in soils for up to a year causing several environmental and health problems. This study aimed to investigate ATZ degradation catalyzed by manganese porphyrins as biomimetic cytochrome P450 models.

The synthetic peptide LyeTxI-b derived from Lycosa erythrognatha spider venom is cytotoxic to U-87 MG glioblastoma cells.

Antimicrobial peptides present a broad spectrum of therapeutic applications, including their use as anticancer peptides. These peptides have as target microbial, normal, and cancerous cells. The oncological properties of these peptides may occur by membranolytic mechanisms or non-membranolytics.

Ciprofloxacin degradation by first-, second-, and third-generation manganese porphyrins.

A range of hydrophobic first-, second-, and third-generation manganese porphyrins (MnPs) was investigated as cytochrome P450 models for degradation of the antibiotic ciprofloxacin (CIP). The experiments were carried out under mild conditions; oxidants such as iodosylbenzene (PhIO), HO, and meta-chloroperbenzoic acid were employed. The PhIO system yielded the best results: CIP degradation ranged between 56% and 76%.

Correlation of structural features of novel 1,2,3-triazoles with their neurotoxic and tumoricidal properties.

Triazoles are interesting templates for novel chemotherapeutic drugs. We synthesized here 17 1,3,4-substituted-1,2,3-triazoles that differed in their 1'-substituent (variable alkyl chain lengths C3-C12), the 3'-substituent (no substituent, -methyl or -propyl) or the salt form obtained. Several of the compounds were cytotoxic (μM range) for tumor cells (HL-60, Jurkat, MCF-7, HCT-116), and when the effect was compared to non-transformed cells (Vero), selectivity ratios of up to 23-fold were obtained.

In vivo and in vitro activity of a bis-arylidenecyclo-alkanone against fluconazole-susceptible and -resistant isolates of Candida albicans.

Objectives: Candida albicans is a commensal organism and opportunistic pathogen associated both with superficial (mucosal and cutaneous) and systemic infections. Extensive use of antifungal agents has led to reduced susceptibility to the few existing drugs, which has encouraged the search for novel antifungal agents. Therefore, the present study investigated the antifungal activity of 2,6-bis[(E)-(4-pyridyl)methylidene]cyclohexanone (PMC) against C.

leishmanicidal, antibacterial and antitumour potential of anhydrocochlioquinone A obtained from the fungus sp.

The bioassay-guided fractionation of the ethyl acetate extract of the fungus Cochliobolus sp. highlighted leishmanicidal activity and allowed for anhydrocochlioquinone A (ANDC-A) isolation. MS, 1D and 2D NMR spectra of this compound were in agreement with those published in the literature.

Novel nitroaromatic compound activates autophagy and apoptosis pathways in HL60 cells.

N-(2-butanoyloxyethyl)-4-(chloromethyl)-3-nitrobenzamide (NBCN) is a nitroaromatic bioreducible compound with cytotoxic effects in cancer cell lines. The aim of this work was to investigate the molecular mechanisms involved in cell death promoted by NBCN in HL60 cells. We observed that NBCN treatment increased intracellular ROS and reduced mitochondria membrane potential (ΔΨm).

Cytotoxicity and bacterial membrane destabilization induced by Annona squamosa L. extracts.

This study aimed to further investigate the cytotoxicity against tumor cell lines and several bacterial strains of Annona squamosa and its mode of action. Methanol extracts of A. squamosa leaves (ASL) and seeds (ASS) were used.

Flavonoids Act As Antimicrobials by Binding to Cell Walls.

is an important pathogen in opportunistic infections in humans. The increased incidence of antimicrobial-resistant isolates has highlighted the need for novel and more potent therapies against this microorganism. is known for presenting different compounds with diverse biological activities, such as anti-tumor and immunomodulatory activities.

Improved In Vitro Antileukemic Activity of All-Trans Retinoic Acid Loaded in Cholesteryl Butyrate Solid Lipid Nanoparticles.

All-trans retinoic acid, a hydrophobic drug, has become one of the most successful examples of differentiation agents used for treatment of acute promyelocytic leukemia. On the other hand, histone deacetylase inhibitors, such as cholesteryl butyrate, present differentiating activity and.can potentiate action of drugs such as all-trans retinoic acid.

Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses.

Background: Chronic Chagas disease presents different clinical manifestations ranging from asymptomatic (namely indeterminate) to severe cardiac and/or digestive. Previous results have shown that the immune response plays an important role, although no all mechanisms are understood. Immunoregulatory mechanisms such as apoptosis are important for the control of Chagas disease, possibly affecting the morbidity in chronic clinical forms.

Nanostructured lipid carriers loaded with tributyrin as an alternative to improve anticancer activity of all-trans retinoic acid.

Objectives: All-trans retinoic acid (ATRA) is one of the most successful examples of differentiation agents and histone deacetylase inhibitors, such as tributyrin (TB), are known for their antitumor activity and potentiating action of drugs, such as ATRA. Nanostructured lipid carriers (NLC) represent a promising alternative to the encapsulation of lipophilic drugs such as ATRA. This study aims to develop, characterize and evaluate the cytotoxicity of ATRA-TB-loaded NLC for cancer treatment.

A reduction of viral mRNA, proteins and induction of altered morphogenesis reveals the anti-HTLV-1 activity of the labdane-diterpene myriadenolide in vitro.

Background: Human T-lymphotropic virus 1 (HTLV-1) has been associated with leukemia/lymphoma (ATL) and myelopathy/tropical spastic paraparesis (HAM/TSP), in addition to other inflammatory diseases as well as infection complications. Therapeutic approaches for HTLV-1-related pathologies are limited. The labdane diterpene myriadenolide (AMY) is a natural product that exhibit biological activities, such as anti-inflammatory and antiviral activity as reported for HIV and herpesvirus.

Synthesis of nitroaromatic compounds as potential anticancer agents.

Twenty-seven nitrated and non-nitrated compounds have been synthesized and tested for their growth inhibitory activity on three human cancer cells lines. Fourteen compounds were able to inhibit more than 50% of the growth of at least one of the cancer cell lines and five compounds exhibited high antiproliferative activity on human cancer cell lines (IC50 < 8.5 μM).

HPLC-DAD analysis, antileishmanial, antiproliferative, and antibacterial activities of Lacistema pubescens: an Amazonian medicinal plant.

Species of the genus Lacistema are traditionally used by Brazilian and Peruvian indigenous communities. The present study investigated the in vitro antileishmanial activity against several Leishmania species, cytotoxicity in murine peritoneal macrophages, antiproliferative activity against HL60 and Jurkat cells, and antibacterial activities against seven bacteria strains of the aerial parts of the methanolic crude extract and fractions of Lacistema pubescens. In addition, their chemical profile was also evaluated.

The cytotoxic and proapoptotic activities of hypnophilin are associated with calcium signaling in UACC-62 cells.

Hypnophilin (HNP) is a sesquiterpene that is isolated from Lentinus cf. strigosus and has cytotoxic activities. Here, we studied the calcium signaling and cytotoxic effects of HNP in UACC-62 cells, a human skin melanoma cell line.