Amine-substituted heterocyclic thioamide Cu(I) and Ag(I) complexes as effective anticancer and antibacterial agents targeting the periplasm of E. coli bacteria.

Metal complexes showing dual activity against cancer and bacterial infections are currently the focus of significant interest for their potential in treating life-threatening diseases. Aiming to investigate the impact of ligand substituents on these bioactivity properties of Group 11 d metal complexes, we herein present a series of mononuclear Cu(I) and Ag(I) complexes featuring the bis-NH-substituted heterocyclic thioamide dap2SH (=4,6-diaminopyrimidine-2-thione), namely [AgCl(dap2SH)(PPh)] (1), [CuBr(dap2SH)(PPh)] (2), [CuBr(dap2SH)(xantphos)] (3), [Ag(dap2S)(xantphos)] (4), and [Cu(dap2S)(xantphos)] (5) (xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene). Complexes were characterized by means of different physicochemical methods (i.

In vitro and in silico evaluation of the serrapeptase effect on biofilm and amyloids of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an emerging threat for hospitalized and cystic fibrosis patients. Biofilm, a microbial community embedded in extracellular polymeric substance, fortifies bacteria against the immune system. In biofilms, the expression of functional amyloids is linked with highly aggregative, multi-resistant strains, and chronic infections.

In Silico Approach for the Evaluation of the Potential Antiviral Activity of Extra Virgin Olive Oil (EVOO) Bioactive Constituents Oleuropein and Oleocanthal on Spike Therapeutic Drug Target of SARS-CoV-2.

Since there is an urgent need for novel treatments to combat the current coronavirus disease 2019 (COVID-19) pandemic, in silico molecular docking studies were implemented as an attempt to explore the ability of selected bioactive constituents of extra virgin olive oil (EVOO) to act as potent SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antiviral compounds, aiming to explore their ability to interact with SARS-CoV-2 Spike key therapeutic target protein. Our results suggest that EVOO constituents display substantial capacity for binding and interfering with Spike (S) protein, both wild-type and mutant, via the receptor-binding domain (RBD) of Spike, or other binding targets such as angiotensin-converting enzyme 2 (ACE2) or the RBD-ACE2 protein complex, inhibiting the interaction of the virus with host cells. This in silico study provides useful insights for the understanding of the mechanism of action of the studied compounds at a molecular level.

Extra Virgin Olive Oil consumption from Mild Cognitive Impairment patients attenuates oxidative and nitrative stress reflecting on the reduction of the PARP levels and DNA damage.

Oxidative/nitrative stress that results from the unbalance of the overproduction/clearance of reactive oxygen/nitrogen species (ROS/NOS), originated from a variety of endo- and/or exo-genous sources, can have detrimental effects on DNA and is involved in Alzheimer's disease (AD) pathology. An excellent marker of oxidative DNA lesions is 8-hydroxy-2'-deoxyguanosine (8-OHdG) while of nitrative stress the enzyme NOS2 (Nitric oxide synthase 2). Under massive oxidative stress, poly(ADP-ribose)polymerase 1 (PARP-1) enzyme activity, responsible for restoration of DNA damage, is augmented, DNA repair enzymes are recruited, and cell survival/or death is ensued through PARP-1 activation, which is correlated positively with neurodegenerative diseases.

Copper(II) complexes with non-steroidal anti-inflammatory drugs: Structural characterization, in vitro and in silico biological profile.

Six novel copper(II) complexes with the non-steroidal anti-inflammatory drugs ibuprofen, loxoprofen, fenoprofen and clonixin as ligands were synthesized and characterized by diverse techniques including single-crystal X-ray crystallography. The in vitro scavenging activity of the complexes against 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) free radicals and the ability to reduce HO were studied in the context of the antioxidant activity studies. The complexes may interact with calf-thymus DNA via intercalation as revealed by the techniques employed.

Nickel(II)-meclofenamate complexes: Structure, in vitro and in silico DNA- and albumin-binding studies, antioxidant and anticholinergic activity.

Five novel nickel(II) complexes with the non-steroidal anti-inflammatory drug sodium meclofenamate (Na-mclf) have been synthesized and characterized in the absence or co-existence of the nitrogen-donors imidazole (Himi), 2,2'-bipyridylamine (bipyam), 2,2'-bipyridylketoxime (Hpko) and 2,9-dimethyl-1,10-phenanthroline (neoc); namely [Ni(mclf-O)(Himi)(MeOH)], [Ni(mclf-O)(MeOH)], [Ni(mclf-O)(mclf-O,O')(bipyam)(MeOH)]·0.25MeOH, [Ni(mclf-O,O')(neoc)] and [Ni(mclf-O)(Hpko-N,N')]·MeOH·0.5HO.

Unraveling the binding mechanism of an Oxovanadium(IV) - Curcumin complex on albumin, DNA and DNA gyrase by in vitro and in silico studies and evaluation of its hemocompatibility.

An oxovanadium(IV) - curcumin based complex, viz. [VO(cur)(2,2´-bipy)(HO)] where cur is curcumin and bipy is bipyridine, previously synthesized, has been studied for interaction with albumin and DNA. Fluorescence emission spectroscopy was used to evaluate the interaction of the complex with bovine serum albumin (BSA) and the BSA-binding constant (K) was calculated to be 2.

Synthesis, structural determination, in vitro and in silico biological evaluation of divalent or trivalent cobalt complexes with indomethacin.

The interaction of cobalt chloride with the non-steroidal anti-inflammatory drug indomethacin (Hindo) led to the formation of the polymeric complex [Co(indo-O)(HO)(μ-Cl)]·n(MeOH·HO) bearing one chlorido bridge between the cobalt atoms. The presence of the nitrogen-donor co-ligands 2,2'-bipyridine (bipy), 2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen) or 1H-imidazole (Himi) resulted in the isolation of complexes [Co(μ-indo-O,O')(indo-O)(bipy)(μ-HO)]·3.3MeOH, [Co(indo-O,O')(bipyam)]·0.

Structure and biological evaluation of pyridine-2-carboxamidine copper(II) complex resulting from N'-(4-nitrophenylsulfonyloxy)2-pyridine-carboxamidoxime.

The interaction of Cu(NO)·3HO with the sulfonyl o-pyridine carboxamidoxime N'-(4-nitrophenylsulfonyloxy)picolinimidamide (L) resulted in the mononuclear complex [Cu(L)](L) (1), where L = pyridine-2-carboxamidine ligand and (L) = 4-nitrobenzenesulfonate anion derived from the homolytic cleavage of the NO bond of L. The complex was characterized by diverse techniques including single-crystal X-ray crystallography. From the antimicrobial tests performed, complex 1 seems to be active against gram-negative bacterial strains.

A palladium(II) complex with the Schiff base 4-chloro-2-(N-ethyliminomethyl)-phenol: Synthesis, structural characterization, and in vitro and in silico biological activity studies.

The synthesis and characterization of the Pd(II) complex of the formula [Pd(L)] 1 with the Schiff base 4-chloro-2-(N-ethyliminomethyl)-phenol (HL) as derived in situ via the condensation reaction of 5-chloro-salicylaldehyde and ethylamine was undertaken. The structure of 1 was verified by single-crystal X-ray crystallography. The ability of 1 to interact with calf-thymus (CT) DNA was studied by UV-vis and viscosity experiments, and its ability to displace ethidium bromide (EB) from the DNA-EB conjugate was revealed by fluorescence spectroscopy.

Palladium(II) complexes with salicylaldehyde ligands: Synthesis, characterization, structure, in vitro and in silico study of the interaction with calf-thymus DNA and albumins.

The synthesis and characterization of four palladium(II) complexes with substituted salicylaldehydes (X-saloH) having the general formula [Pd(X-salo)] was undertaken. The complexes are formulated as [Pd(3-OCH-salo)] 1, [Pd(5-NO-salo)] 2, [Pd(5-Cl-salo)] 3, and [Pd(5-Br-salo)] 4. The structure of complex 1 was verified by single-crystal X-ray crystallography.

In vitro and in silico study of the biological activity of manganese(III) inverse-[9-MC-3]-metallacrowns and manganese(II) complexes with the anti-inflammatory drugs diclofenac or indomethacin.

In the present contribution, the biological properties of four manganese complexes with the non-steroidal anti-inflammatory drugs sodium diclofenac (Nadicl) or indomethacin (Hindo) in the presence or absence of salicylaldoxime (Ηsao), i.e. [Μn(O)(dicl)(sao)(CHOH)] 1, [Μn(O)(indo)(sao)(HO)], 2, [Μn(dicl)(CHOH)], 3, and [Μn(indo)(CHOH)], 4 are presented.

Amplifying and broadening the cytotoxic profile of quercetin in cancer cell lines through bioconjugation.

Quercetin is a flavonoid presenting cytotoxicity against different cancer cell lines. We hypothesized that its core could serve as a scaffold for generating more potent compounds. A quercetin-alanine bioconjugate was synthesized, its cellular internalization was monitored through confocal microscopy and its cytotoxic activity was explored against ten different cell lines.

Rational design and structure-activity relationship studies of quercetin-amino acid hybrids targeting the anti-apoptotic protein Bcl-xL.

Anti-apoptotic proteins, like the Bcl-2 family proteins, present an important therapeutic cancer drug target. Their activity is orchestrated through neutralization upon interaction of pro-apoptotic protein counterparts that leads to immortality of cancer cells. Therefore, generating compounds targeting these proteins is of immense therapeutic importance.

Adriamycin in combination with dexamethasone and octreotide lacks activity on the treatment of a 4T1 metastatic breast cancer model.

The aim of this study was to evaluate whether the palliative treatment for metastatic disease with dexamethasone (DEX) plus octreotide (OCT) can improve the anticancer effects of the standard treatment with adriamycin (ADR) on a 4T1 metastatic breast cancer (MBC) model. 4T1 cells were first characterized for the expression of the somatostatin receptors 1-5 and were then inoculated onto the femur of BALB/C mice. Investigation protocols used 4T1 cell proliferation and invasion assays, analysis of radiographic images of the bone metastatic lesions, and overall survival of the diseased animals.

Overview on the current status on virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part II.

Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Nowadays, new generation of anticancer drugs, able to inhibit more than one pathway, is believed to play a major role in contemporary anticancer drug research. In this way, polypharmacology, focusing on multi-target drugs, has emerged as a new paradigm in drug discovery.

Overview on the current status of virtual high-throughput screening and combinatorial chemistry approaches in multi-target anticancer drug discovery; Part I.

Conventional drug design embraces the "one gene, one drug, one disease" philosophy. Nowadays, new generation of anti- cancer drugs, able to inhibit more than one pathway, is believed to play a major role in contemporary anticancer drug research. In this way, polypharmacology, focusing on multi-target drugs, has emerged as a new paradigm in drug discovery.

Safranal, a Crocus sativus L constituent suppresses the growth of K-562 cells of chronic myelogenous leukemia. In silico and in vitro study.

Crocin, a main constituent of Crocus sativus L (saffron), has been found to inhibit the growth of K-562 human chronic myelogenous leukemia (CML) cells expressing Bcr-Abl protein tyrosine kinase activity. The aim of our study is to investigate the ability of the bioactive saffron's constituents, crocin (CRC) and safranal (SFR), to inhibit the Bcr-Abl protein activity employing an in silico approach, as well as the in vitro effect of these compounds on K-562 growth and gene expression of Bcr-Abl. In silico molecular docking studies revealed that mostly SFR can be attached to Bcr-Abl protein, positioned inside the protein's binding cavity at the same place with the drug used in the treatment of CML, imatinib mesylate (IM).

Anticarcinogenic activity of polyphenolic extracts from grape stems against breast, colon, renal and thyroid cancer cells.

A major part of the wineries' wastes is composed of grape stems which are discarded mainly in open fields and cause environmental problems due mainly to their high polyphenolic content. The grape stem extracts' use as a source of high added value polyphenols presents great interest because this combines a profitable venture with environmental protection close to wine-producing zones. In the present study, at first, the Total Polyphenolic Content (TPC) and the polyphenolic composition of grape stem extracts from four different Greek Vitis vinifera varieties were determined by HPLC methods.

Effect of cobalt(II) complexes with dipyridylamine and salicylaldehydes on cultured tumor and non-tumor cells: synthesis, crystal structure investigations and biological activity.

The synthesis of eight mixed-ligand cobalt(II) complexes with 2,2'-dipyridylamine (dpamH) and substituted salicylaldehydes (X-saloH) was undertaken in an effort to discover new compounds with anticancer activity. The complexes with the general formula [Co(dpamH)(2)(X-salo)]Y, (Y=Br or Cl) were characterized by elemental analyses, FT-IR and UV-visible spectroscopy, magnetic and conductivity measurements. The structures of two of them [Co(dpamH)(2)(5-CH(3)-salo)]Br and [Co(dpamH)(2)(3-OCH(3)-salo)]Cl, as well as of the precursors [Co(dpamH)(3)]Br(2) and [Co(dpamH)(2)Cl(H(2)O)]Cl, were determined by X-ray crystallography revealing octahedral coordination of cobalt(II) and mononuclear complexes.

Saffron as a source of novel acetylcholinesterase inhibitors: molecular docking and in vitro enzymatic studies.

Inhibitors of acetylcholine breakdown by acetylcholinesterase (AChE) constitute the main therapeutic modality for Alzheimer's disease. In the search for natural products with inhibitory action on AChE, this study investigated the activity of saffron extract and its constituents by in vitro enzymatic and molecular docking studies. Saffron has been used in traditional medicine against Alzheimer's disease.

In silico/in vitro study of hybrid D-modified steroidal alkylator anticancer activity using uridine phosphorylase as target protein.

Background: In order to reduce toxicity and to enhance anticancer activity of nitrogen mustards, three hybrid steroidal esters were synthesized and tested in vitro against human pancreatic cancer cells expressing uridine phosphorylase (UPase). The inhibition potency against a target protein implicated in the chemotherapy of solid tumors, such as UPase, is of fundamental importance in the design and synthesis of new anticancer drugs.

Materials And Methods: MTT colorimetric assay and molecular docking were employed for the in vitro and in silico drug evaluation, respectively.