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Antibacterial mechanism of hypocrellin against Ralstonia solanacearum in tobacco and its modulation of the endophytic microbiome.

The photosensitive compound hypocrellin, derived from the traditional Chinese medicinal fungus Shiraia bambusicola Henn., shows potential as a novel pesticide. To evaluate its efficacy against bacterial wilt disease caused by Ralstonia solanacearum in tobacco, this study examined its antibacterial mechanisms through in vitro experiments and analyzed their impact on tobacco endophytic microbiota. An optimized hypocrellin offering a promising sustainable formulation-with a 2:3 ratio of hypocrellin A to hypocrellin B-was developed for enhanced antibacterial activity, and its interaction with bact

Antibacterial potential, DNA binding and molecular docking investigations of newly green synthesized zinc oxide/chitosan/vancomycin nanocomposite using Bacillus licheniformis ATCC 4527 against some drug-resistant bacteria.

BACKGROUND: The increasing crisis of multidrug-resistant (MDR) bacteria requires the creation of new, highly effective, and safe antibacterial agents. This study introduces a simple and cost-effective green synthesis method for a novel zinc oxide/chitosan/vancomycin (ZnO/CS/VA) nanocomposite to improve antibacterial activity against priority MDR strains. Zinc oxide nanoparticles (ZnO NPs) were biosynthesized using Bacillus licheniformis ATCC 4527 and then combined with vancomycin (VA) and chitosan (CS) in an environmentally friendly process. Transmission electron microscopy (TEM), Fourier tran

Substitution Kinetics, DNA/BSA Interactions, Cytotoxicity Evaluation and Computational Analysis of [bis-(azaaryl)amine)Pt(II)/Pd(II)Cl] Complexes, Azaaryl = Quinoline or Phenanthridine.

The search for metal-based anticancer agents with improved efficacy and reduced side effects is ongoing. The activities of these anticancer drugs depend on their aqueous stability, substitutional reactivity at target sites (cytotoxicity) and nontarget sites (toxicity), as well as their transportation and cell bioavailability. In this study, six square-planar Pt(II) and Pd(II) complexes (Pt/PdL1Cl-3), all bearing the bis(azaaryl)amine (azaaryl = quinoline or phenanthridine) chelating ligands, were synthesised and characterised by various spectroscopic methods. Their biochemical interactions wit

Bis(triazinyl)pyridine complexes of Pt(II) and Pd(II): studies of the nucleophilic substitution reactions, DNA/HSA interactions, molecular docking and biological activity.

Four new complexes of Pt(II) and Pd(II), [Pd(L1)Cl]Cl 1, [Pd(L2)Cl]Cl 2, [Pt(L1)Cl]Cl 3 and [Pt(L2)Cl]Cl 4 (where L1 = 2,6-bis(5,6-diphenyl-1,2,4-triazin-3-yl)pyridine and L2 = 2,6-bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine), were synthesized. Characterization of the complexes was performed using elemental analysis, IR, 1H NMR spectroscopy and MALDI-TOF mass spectrometry. The substitution reactions of 1-4 complexes with L-methionine (L-met), L-cysteine (L-cys) and guanosine-5'-monophosphate (5'-GMP), were studied spectrophotometrically at physiological conditions. Complexes with ligand L1 (1

Synthesis, structural characterization, and biological studies of ATBS-M complexes (M(II) = Cu, Co, Ni, and Mn): Access for promising antibiotics and anticancer agents.

A new bidentate Schiff base ligand (ATBS [4-bromo-2-(thiazole-2-yliminomethyl)phenol]) was synthesized via the condensation reaction of 2-aminothiazole with 5-bromosalicylaldehyde in ethanol. The reaction of ATBS with transition metal salts of Cu(II), Co(II), Ni(II), and Mn(II) afforded the corresponding ATBS-M complexes. Results from physicochemical and spectral analyses, such as elemental analysis, infrared, UV-Vis spectroscopy, magnetic susceptibility, and molar conductance, revealed a nonelectrolytic nature with octahedral (Oh ) geometry and a metal/ligand ratio of 1:2 for Cu(II), Co(II),

Voreloxin, a first-in-class anticancer quinolone derivative, in relapsed/refractory solid tumors: a report on two dosing schedules.

PURPOSE: Voreloxin, a novel replication-dependent DNA-damaging agent, intercalates DNA and inhibits topoisomerase II. Voreloxin induces site-selective DNA double-strand breaks and apoptosis. We report the phase 1 experience of voreloxin in patients with relapsed/refractory solid tumors, including dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), pharmacokinetics, and clinical activity. EXPERIMENTAL DESIGN: Two dose-escalation studies evaluated voreloxin administered i.v. every 3 weeks (SPO-0001) or weekly for 3 weeks every 28 days (SPO-0002). In SPO-0001, patients were classified as

[Sialadenosis of the parotid gland. Ultrastructural, clinical and experimental findings in disturbances of secretion (author's transl)].

Among the secretory disturbances ("Dyschylien") of salivary glands the sialadenosis of the parotid gland is a clinic and a morphologic definited entity. The typical clinical symptom is a bilateral, often recurrent, and painless swelling of the parotid gland. The characteristic pathological findings consist in an acinar cell hypertrophy without any inflammatory signs. According to this definition, sialadenosis has to be separated from those diseases of salivary glands, which are primarily altered by inflammation of the salivary tissue with secondary secretory disturbances. From flinical point o

New Pd(II)-pincer type complexes as potential antitumor drugs: synthesis, nucleophilic substitution reactions, DNA/HSA interaction, molecular docking study and cytotoxic activity.

Two new complexes of Pd(II), [Pd(L1)Cl]Cl (Pd1) and [Pd(L2)Cl]Cl (Pd2), (where L1 = N2,N6-bis(5-methylthiazol-2-yl)pyridine-2,6-dicarboxamide and L2 = N2,N6-di(benzo[d]thiazol-2-yl)pyridine-2.6-dicarboxamide) were synthesized. Characterization of the complexes was performed using elemental analysis, IR, 1H NMR spectroscopy and MALDI-TOF mass spectrometry. The nucleophilic substitution reactions of complexes with L-Methionine (L-Met), L-Cysteine (L-Cys) and guanosine-5'-monophosphate (5'-GMP) were studied by stopped-flow method at physiological conditions (pH = 7.2 and 37 °C). Complex Pd1 was m

Copper-assisted anticancer activity of hydroxycinnamic acid terpyridine conjugates on triple-negative breast cancer.

The development of active therapeutic agents to treat highly metastatic cancer while minimizing damage to healthy cells is of utmost importance. Due to potential antioxidant properties, hydroxycinnamic acid derivatives (caffeic acid and p-coumaric acids) were found to inhibit highly metastatic breast cancer cell growth both in vitro and in vivo without much effect on normal cells. Especially due to the structure-activity relationships, ester and amide derivatives of hydroxycinnamic acids are reported to gain much higher radical scavenging ability than their naked hydroxycinnamic acid analogs l

Genome composition in Venezuelan spiny-rats of the genus Proechimys(Rodentia, Echimyidae). I. Genome size, C-heterochromatin and repetitive DNAs in situ hybridization patterns.

The genome sizes of the Venezuelan spiny-rats Proechimys guairae guairae (2n = 48) and P. trinitatis (2n = 62) were evaluated and proved to be 12.5 +/- 0.5 pg and 12.6 +/- 0.3 pg respectively, the highest so far recorded among mammals; also the C-heterochromatin (32.7%, Coefficient of Variation [CV] 3.8 and 35.8%, CV 4.4) and GC (44.2%, CV 2.7 and 43.6%, CV 2.9) contents are very high. Highly repetitive (rep) DNAs were isolated from restriction enzyme digested genomic DNAs of both species. The intra- and inter-specific chromosomal allocations of these rep DNAs were analyzed by direct and cross

Synthesis, Structural Investigations, Molecular Docking, and Anticancer Activity of Some Novel Schiff Bases and Their Uranyl Complexes.

Three novel 2-aminopyrazine Schiff bases derived from salicylaldehyde derivatives and their uranyl complexes were synthesized and characterized by elemental analysis, UV-vis, FTIR, molar conductance, and thermal gravimetric analysis (TGA). The proposed structures were optimized using density functional theory (DFT/B3LYP) and 6-311G ∗(d,p) basis sets. All uranyl complexes are soluble in DMSO and have low molar conductance, which indicates that all the complexes are nonelectrolytes. The DNA binding of those Schiff bases and their uranyl complexes was studied using UV-vis spectroscopy, and screen

Open complex formation around a lesion during nucleotide excision repair provides a structure for cleavage by human XPG protein.

Human XPG nuclease makes the 3' incision during nucleotide excision repair of DNA. The enzyme cleaves model DNA bubble structures specifically near the junction of unpaired DNA with a duplex region. It is not yet known, however, whether an unpaired structure is an intermediate during actual DNA repair. We find here that XPG requires opening of >5 bp for efficient cleavage. To seek direct evidence for formation of an open structure around a lesion in DNA during a nucleotide excision repair reaction in vitro, KMnO4 footprinting experiments were performed on a damaged DNA molecule bearing a uniqu

Anticancer DNA intercalators cause p53-dependent mitochondrial DNA nucleoid re-modelling.

Many anticancer drugs, such as doxorubicin (DXR), intercalate into nuclear DNA of cancer cells, thereby inhibiting their growth. However, it is not well understood how such drugs interact with mitochondrial DNA (mtDNA). Using cell and molecular studies of cultured cells, we show that DXR and other DNA intercalators, such as ethidium bromide, can rapidly intercalate into mtDNA within living cells, causing aggregation of mtDNA nucleoids and altering the distribution of nucleoid proteins. Remodelled nucleoids excluded DXR and maintained mtDNA synthesis, whereas non-remodelled nucleoids became hea

Dectin-1-Targeted Antifungal Liposomes Exhibit Enhanced Efficacy.

Aspergillus species cause pulmonary invasive aspergillosis resulting in nearly 100,000 deaths each year. Patients at the greatest risk of developing life-threatening aspergillosis have weakened immune systems and/or various lung disorders. Patients are treated with antifungals such as amphotericin B (AmB), caspofungin acetate, or triazoles (itraconazole, voriconazole, etc.), but these antifungal agents have serious limitations due to lack of sufficient fungicidal effect and human toxicity. Liposomes with AmB intercalated into the lipid membrane (AmB-LLs; available commercially as AmBisome) hav

Fluorescence-based methods for evaluating the RNA affinity and specificity of HIV-1 Rev-RRE inhibitors.

RNA plays a pivotal role in the replication of all organisms, including viral and bacterial pathogens. The development of small molecules that selectively interfere with undesired RNA activity is a promising new direction for drug design. Currently, there are no anti-HIV treatments that target nucleic acids. This article presents the HIV-1 Rev response element (RRE) as an important focus for the development of antiviral agents that target RNA. The Rev binding site on the RRE is highly conserved, even between different groups of HIV-1 isolates. Compounds that inhibit HIV replication by binding

Unexpected formation of parallel duplex in GAA and TTC trinucleotide repeats of Friedreich's ataxia.

The onset and progress of Friedreich's ataxia (FRDA) is associated with the genetic instability of the (GAA).(TTC) trinucleotide repeats located within the frataxin gene. The instability of these repeats may involve the formation of an alternative DNA structure. Poly-purine (R)/poly-pyrimidine (Y) sequences typically form triplex DNA structures which may contribute to genetic instability. Conventional wisdom suggested that triplex structures formed by these poly-purine (R)/poly-pyrimidine (Y) sequences may contribute to their genetic instability. Here, we report the characterization of the sin

Targeted synthesis of a trimethoxyphenyltetrahydropyrimidine analogue designed as a DNA intercalator: in silico, multi-spectroscopic, thermodynamic, and in vitro approaches.

Based on the rational design of DNA intercalators and Topo-II inhibitors and taking into consideration the main pharmacophoric features of doxorubicin (Dox) as a reference standard, we theoretically designed novel substituted tetrahydropyrimidine analogues (T1-35). The designed analogues (T1-35) were investigated for their inhibitory potential towards the hybrid DNA and Topo-II target receptor using molecular docking. Interestingly, the theoretically designed analogue T30 with a 3,4,5-trimethoxy phenyl side chain was found to be the superior candidate, achieving a binding score of -7.06 kcal m

Chemotherapeutic agents for the treatment of hepatocellular carcinoma: efficacy and mode of action.

Hepatocellular carcinoma (HCC) is a dreaded malignancy that every year causes half a million deaths worldwide. Being an aggressive cancer, its incidence exceeds 700,000 new cases per year worldwide with a median survival of 6-8 months. Despite advances in prognosis and early detection, effective HCC chemoprevention or treatment strategies are still lacking, therefore its dismal survival rate remains largely unchanged. This review will characterize currently available chemotherapeutic drugs used in the treatment of HCC. The respective mode(s) of action, side effects and recommendations will be

New insights into the activities and toxicities of the old anticancer drug doxorubicin.

The anthracycline drug doxorubicin is among the most used-and useful-chemotherapeutics. While doxorubicin is highly effective in the treatment of various hematopoietic malignancies and solid tumours, its application is limited by severe adverse effects, including irreversible cardiotoxicity, therapy-related malignancies and gonadotoxicity. This continues to motivate investigation into the mechanisms of anthracycline activities and toxicities, with the aim to overcome the latter without sacrificing the former. It has long been appreciated that doxorubicin causes DNA double-strand breaks due to

Совпадение в полном тексте источника
… Pommier Y, Schwartz RE, Zwelling LA & Kohn KW (1985) Effects of DNA intercalating agents on topoisomerase‐Ii induced DNA strand cleavage in isolated mammalian‐cell nuclei. Biochemistry‐Us 24, 6406–6410. 21. …

DNA Binding, DNA Photocleavage, Molecular Docking Studies and Photo-Induced Effect on Melanoma Cells of 2-Methyl-3-OR Quinazolinone Derivatives.

Thirty 2-methyl-quinazolinone fussed hydroxamic acids (3-OH) and their 3-OEt and 3-OBn derivatives were evaluated for their affinity towards calf-thymus (CT) DNA using UV-vis absorption, viscosity and fluorescence spectroscopy. DNA photocleavage activity was assessed by incubating the compounds with plasmid DNA followed by UV-A and visible light irradiation, which enabled identification of the most potent derivatives active at concentrations of 100 nΜ and 10 μΜ, respectively. Mechanistic studies on the most active compounds indicated the formation of oxygen radical species and a decrease in ef