Anticancer Metallocenes and Metal Complexes of Transition Elements from Groups 4 to 7.

With the progression in the field of bioinorganic chemistry, the role of transition metal complexes as the most widely used therapeutics is becoming a more and more attractive research area. The complexes of transition metals possess a great variety of attractive pharmacological properties, including anticancer, anti-inflammatory, antioxidant, anti-infective, etc., activities. Transition metal complexes have proven to be potential alternatives to biologically active organic compounds, especially as antitumor agents. The performance of metal coordination compounds in living systems is anticipated to differ generally from the action of non-metal-containing drugs and may offer unique diagnostic and/or therapeutic opportunities. In this review, the rapid development and application of metallocenes and metal complexes of elements from Groups 4 to 7 in cancer diagnostics and therapy have been summarized. Most of the heavy metals discussed in the current review are newly discovered metals. That is why the use of their metal-based compounds has attracted a lot of attention concerning their organometallic and coordination chemistry. All of this imposes more systematic studies on their biological activity, biocompatibility, and toxicity and presupposes further investigations.

Coumarin-transition metal complexes with biological activity: current trends and perspectives.

Coumarin (2H-1-benzopyran-2-one) presents the fundamental structure of an enormous class of biologically active compounds of natural, semi-synthetic, and synthetic origin. Extensive efforts are continually being put into the research and development of coumarin derivatives with medicinal properties by the broad scientific community. Transition metal coordination compounds with potential biological activity are a "hot topic" in the modern search for novel drugs. Complexation with transition metals can enhance the physiological effect of a molecule, modify its safety profile, and even imbue it with novel attributes of interest in the fields of medicine and pharmacy. The present review aims to inform the reader of the latest developments in the search for coumarin transition metal complexes with biological activity, their potential applications, and structure-activity relationships, where such can be elucidated. Each section of the present review addresses a certain kind of biological activity (antiproliferative, antioxidant, antimicrobial, etc.), explores the most recent discoveries in the field, and, at the same time, tries to offer useful perspectives for potential future investigations.

Study of the Molecular Architectures of 2-(4-Chlorophenyl)-5-(pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylic Acid Using Their Vibrational Spectra, Quantum Chemical Calculations and Molecular Docking with MMP-2 Receptor.

1,2,3-triazole skeleton is a valuable building block for the discovery of new promising anticancer agents. In the present work, the molecular structure of the synthesized anticancer drug 2-(4-chlorophenyl)-5-(pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylic acid (1b) and its anionic form (2b) was characterized by means of the B3LYP, M06-2X and MP2 quantum chemical methods, optimizing their monomer, cyclic dimer and stacking forms using the Gaussian16 program package. The molecular structure was found to be slightly out of plane. The good agreement between the IR and Raman bands experimentally observed in the solid state with those calculated theoretically confirms the synthesized structures. All of the bands were accurately assigned according to functional calculations (DFT) in the monomer and dimer forms, together with the polynomic scaling equation procedure (PSE). Therefore, the effect of the substituents on the triazole ring and the effect of the chlorine atom on the molecular structure and on the vibrational spectra were evaluated through comparison with its non-substituted form. Through molecular docking calculations, it was evaluated as to how molecule 1b interacts with few amino acids of the MMP-2 metalloproteinase receptor, using Sybyl-X 2.0 software. Thus, the relevance of triazole scaffolds in established hydrogen bond-type interactions was demonstrated.

Structural Study of a La(III) Complex of a 1,2,3-Triazole Ligand with Antioxidant Activity.

The 1,2,3-triazole derivative 2-(4-chlorophenyl)-5-(pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylic acid with potential anticancer activity was used as a ligand in complex formation with the lanthanum(III) ion. The molecular structure and vibrational spectra of the complex were optimized at three DFT levels, and the scaled IR and Raman spectra were compared to the experimental ones. Several scaling procedures were used. Through a detailed analysis, the structure predicted for the newly synthetized La(III) complex was confirmed by the good accordance of the calculated/experimental IR and Raman spectra. The best DFT method appeared to be M06-2X with the Lanl2mb basis set, followed closely by Lanl2dz. The effect of the lanthanide atom on the molecular structure and atomic charge distribution of the triazole ring was evaluated. The potential free radical scavenging activity of both the ligand and the complex was investigated in several radical-generating model systems. The potential mechanisms of antioxidant action (hydrogen atom transfer (HAT) and single-electron transfer (SET)) were elucidated.

Peculiarities of the Spatial and Electronic Structure of 2-Aryl-1,2,3-Triazol-5-Carboxylic Acids and Their Salts on the Basis of Spectral Studies and DFT Calculations.

The molecular structure and vibrational spectra of six 1,2,3-triazoles-containing molecules with possible anticancer activity were investigated. For two of them, the optimized geometry was determined in the monomer, cyclic dimer and stacking forms using the B3LYP, M06-2X and MP2 methods implemented in the GAUSSIAN-16 program package. The effect of the para-substitution on the aryl ring was evaluated based on changes in the molecular structure and atomic charge distribution of the triazole ring. An increment in the positive N4 charge was linearly related to a decrease in both the aryl ring and the carboxylic group rotation, with respect to the triazole ring, and by contrast, to an increment in the pyrrolidine ring rotation. Anionic formation had a larger effect on the triazole ring structure than the electronic nature of the different substituents on the aryl ring. Several relationships were obtained that could facilitate the selection of substituents on the triazole ring for their further synthesis. The observed IR and Raman bands in the solid state of two of these compounds were accurately assigned according to monomer and dimer form calculations, together with the polynomic scaling equation procedure (PSE). The large red-shift of the C=O stretching mode indicates that strong H-bonds in the dimer form appear in the solid state through this group.

1,2,3-Triazoles and their metal chelates with antimicrobial activity.

The emergence of drug-resistant bacterial and fungal pathogens has highlighted the urgent need of innovative antimicrobial therapeutics. Transition metal complexes with biologically active ligands (coumarins, terpyridines, triazoles, uracils, etc.) have long been investigated for antimicrobial activity. 1,2,3-Triazoles and their molecular derivatives are well known for a plethora of physiological activities, including antibacterial and antifungal. The aim of the present mini-review is to inform the reader about research conducted on potential antimicrobial 1,2,3-triazole complexes with transition metals. What the authors find surprising is how little such research and experimentation has actually been performed and reported in scientific literature. The goal is to highlight research efforts up to now and impress upon the reader the vast perspectives for novel, effective medicinal substances hidden in this yet unexplored field.

Photocaging of Carboxylic Function Bearing Biomolecules by New Thiazole Derived Fluorophore.

The design and synthesis of a new fluorophore containing an arylidene thiazole scaffold resulted in a compound with good photophysical characteristics. Furthermore, the thiazole C5-methyl group was easily modified into specific functional groups (CH2 Br and CH2 OH) for the formation of a series of photocourier molecules containing model compounds (benzoic acids), as well as prodrugs, including salicylic acid, caffeic acid, and chlorambucil via a "benzyl" linker. Spectral characteristics (1 H, 13 C NMR, and high-resolution mass spectra) corresponded to the proposed structures. The photocourier molecules demonstrated absorption with high values of coefficient of molar extinction, exhibited contrasting green emission, and showed good dark stability. The mechanism of the photorelease was investigated through spectral analysis, HPLC-HRMS, and supported by TD-DFT calculations. The photoheterolysis and elimination of carboxylic acids were proved to occur in the excited state, yielding a carbocation as an intermediate moiety. The fluorophore structure provided stability to the carbocation through the delocalization of the positive charge via resonance structures. Viability assessment of Vero cells using the MTT-test confirmed the weak cytotoxicity of prodrugs without irradiation and it increase upon UV-light.

From Basics of Coordination Chemistry to Understanding Cisplatin-analogue Pt Drugs.

BACKGROUND: Cisplatin, a platinum complex discovered by Rosenberg in 1969, has long been known as the first metal-based anticancer agent. Since then, various similar derivatives of cisplatin have been investigated for pharmacological activity, and the approved complexes have been applied as drugs. OBJECTIVES: The aims of the current study are: 1) to summarize the advantages and dose-limiting effects of the approved and unapproved chemotherapy platinum cytostatics, 2) to develop new strategies for the development of platinum anticancer drugs, and 3) to clarify the important factors for the mechanism of action of platinum complexes. METHODS: A search was conducted in the literature databases, and the obtained information was summarized and analyzed. RESULTS: Myelosuppression is the main dose-limiting effect and the reason for the disapproval of platinum complexes, such as picoplatin, enloplatin, miboplatin, sebriplatin, zeniplatin, spiroplatin, iproplatin, and ormaplatin. From the basic point of view of inorganic coordination chemistry, such as theoretical calculations, crystal structures of model complexes, docking structures with nucleic acid molecules, spectroscopy, and biological aspects, the importance of physicochemical properties of inorganic platinum complexes for their mechanism of action has been indicated. Spectroscopic methods, such as FTIR, NMR, X-ray crystal structure analysis, and fluorescence microscopy, are important for the investigation of the conformational changes in the binding of platinum complexes and DNA. CONCLUSION: In the development of platinum complexes, strong anti-cancer drug activity, low toxicity, and resistance can be obtained by the application of polynuclear platinum agents, complexes with targeted activity, and nanoparticle formulations. Electronic structure, stereochemical, and thermodynamic properties are essential for understanding the reaction mechanism of platinum complexes.

Experimental IR, Raman, and UV-Vis Spectra DFT Structural and Conformational Studies: Bioactivity and Solvent Effect on Molecular Properties of Methyl-Eugenol.

Structural, conformational, and spectroscopic investigations of methyl-eugenol were made theoretically at the B3LYP-6-311++G**level. Experimental IR, Raman, and UV-vis spectra were investigated and analyzed in light of the computed quantities. Conformational analysis was carried out with the help of total energy vs. dihedral angle curves for different tops, yielding 21 stable conformers, out of which only two have energies below the room temperature relative to the lowest energy conformer. The effect of the solvent on different molecular characteristics was investigated theoretically. MEP and HOMO-LUMO analysis were carried out and barrier heights and bioactivity scores were determined. The present investigation suggests that the molecule has three active sites with moderate bioactivity. The solvent-solute interaction is found to be dominant in the vicinity of the methoxy moieties.

Combined NMR Spectroscopy and Quantum-Chemical Calculations in Fluorescent 1,2,3-Triazole-4-carboxylic Acids Fine Structures Analysis.

The peculiarities of the optical properties of 2-aryl-1,2,3-triazole acids and their sodium salts were investigated in different solvents (1,4-dioxane, dimethyl sulfoxide DMSO, methanol MeOH) and in mixtures with water. The results were discussed in terms of the molecular structure formed by inter- and intramolecular noncovalent interactions (NCIs) and their ability to ionize in anions. Theoretical calculations using the Time-Dependent Density Functional Theory (TDDFT) were carried out in different solvents to support the results. In polar and nonpolar solvents (DMSO, 1,4-dioxane), fluorescence was provided by strong neutral associates. Protic MeOH can weaken the acid molecules' association, forming other fluorescent species. The fluorescent species in water exhibited similar optical characteristics to those of triazole salts; therefore, their anionic character can be assumed. Experimental 1H and 13C-NMR spectra were compared to their corresponding calculated spectra using the Gauge-Independent Atomic Orbital (GIAO) method and several relationships were established. All these findings showed that the obtained photophysical properties of the 2-aryl-1,2,3-triazole acids noticeably depend on the environment and, therefore, are good candidates as sensors for the identification of analytes with labile protons.

Antioxidant Activity of Coumarins and Their Metal Complexes.

Ubiquitously present in plant life, coumarins, as a class of phenolic compounds, have multiple applications-in everyday life, in organic synthesis, in medicine and many others. Coumarins are well known for their broad spectrum of physiological effects. The specific structure of the coumarin scaffold involves a conjugated system with excellent charge and electron transport properties. The antioxidant activity of natural coumarins has been a subject of intense study for at least two decades. Significant research into the antioxidant behavior of natural/semi-synthetic coumarins and their complexes has been carried out and published in scientific literature. The authors of this review have noted that, during the past five years, research efforts seem to have been focused on the synthesis and examination of synthetic coumarin derivatives with the aim to produce potential drugs with enhanced, modified or entirely novel effects. As many pathologies are associated with oxidative stress, coumarin-based compounds could be excellent candidates for novel medicinal molecules. The present review aims to inform the reader on some prominent results from investigations into the antioxidant properties of novel coumarin compounds over the past five years.

Recent Trends in the Development of Novel Metal-Based Antineoplastic Drugs.

Since the accidental discovery of the anticancer properties of cisplatin more than half a century ago, significant efforts by the broad scientific community have been and are currently being invested into the search for metal complexes with antitumor activity. Coordination compounds of transition metals such as platinum (Pt), ruthenium (Ru) and gold (Au) have proven their effectiveness as diagnostic and/or antiproliferative agents. In recent years, experimental work on the potential applications of elements including lanthanum (La) and the post-transition metal gallium (Ga) in the field of oncology has been gaining traction. The authors of the present review article aim to help the reader "catch up" with some of the latest developments in the vast subject of coordination compounds in oncology. Herewith is offered a review of the published scientific literature on anticancer coordination compounds of Pt, Ru, Au, Ga and La that has been released over the past three years with the hope readers find the following article informative and helpful.

5-Amino-2-aryl-2H-1,2,3-triazole-4-carboxamides: Unique AIEE-gens and selective Hg2+ fluorosensors.

A series of fluorescent sensors based on small molecule were designed and fully characterised, demonstrating AIEE effect and revealing an outstanding ability to selectively detect Hg2+ ions. The structural and electronic properties were studied through quantum chemical calculations at (Time-Dependent) Density Functional Theory ((TD)-DFT) level. Carboxamides of 2-Aryl-1,2,3-Triazoles (CATs) showed significant differences in their photophysical properties depending on the structure of the substituent at amino function on the C5-atom in the heterocycle. When the tert-cycloalkylamino group (pyrrolidine, piperidine, azepane) was attached, the triazoles exhibited highly intensive blue fluorescence, with quantum yields (QYs) up to 95 % and lifetime up to 6.9 ns in different solvents, whereas the QYs of congeners bearing secondary alkylaminogroups (viz., NHMe, NHC6H11-cyclo) indicate low QYs (1-10 %). Nevertheless, all types of the obtained fluorophores demonstrated excellent AIEE effect and formed fluorescent nanoparticles in a binary mixtures of organic solvents and water. The introduction of the carboxamide function enhances the sensing properties of 2-aryl-1,2,3-triazoles, providing a selective fluorescence quenching reaction in the presence of Hg2+. The fluorescence intensity of the CATs declines with the addition of 1.0 eq. of Hg2+ into DMSO-water (v/v, 1:9). The other cations used did not induce any appreciable changes in fluorescence intensity. The CATs form a complex with Hg2+ with highly specific detection for Hg2+ over other competitive metal ions: the detection limits were determined to be 0.23 and 0.15 µM for the CATs 1b and 2c. The reverse effect was registered with the addition of ethylene diamine sodium salt; meanwhile, the CATs demonstrated more effective coordination with Hg2+ in comparison with cysteine. This last finding, as well as the ability to detect Hg2+, is very valuable for application within biology and medicine.

Can the Therapeutic Spectrum of Probiotics be Extended: Exploring Potential of Gut Microbiome.

Natural therapeutic microorganisms provide a potent alternative healthcare treatment nowadays, with the potential to prevent several human diseases. These health-boosting living organisms, probiotics mostly belong to Gram-positive bacteria such as Lactobacillus, Bifidobacterium, Streptococcus, Saccharomyces, Bacillus and Enterococcus. Initiated almost a century ago, the probiotic application has come a long way. The present review is focused on the potential therapeutic role of probiotics in ameliorating multiple infections, such as upper respiratory tract infections and viral respiratory infections, including COVID-19; liver diseases and hepatic encephalopathy; neurological and psychiatric disorders; autoimmune diseases, particularly rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis. Apart from these, the therapeutic exacerbations of probiotics in urinary tract infections have been extremely promising, and several approaches are reviewed and presented here. We also present upcoming and new thrust areas where probiotic therapeutic interventions are showing promising results, like faecal microbial transplant and vaginal microbial transplant.

An Integrated Approach to Identify Intrinsically Disordered Regions in Osteopontin with its Interacting Network in Rheumatoid Arthritis.

BACKGROUND: Credentials of molecular diagnostic approaches are an important goal. Since protein-protein interaction (PPI) network analysis is an apposite method for molecular valuation, a PPI grid related to Intrinsically Disordered Proteins (IDPs) of RA was targeted in the present research. AIM: The aim of the study is to analyse the role of highly disordered proteins and their functional parameters in causing Rheumatoid Arthritis (RA). METHODS: Cytoscape software helped in identifying molecular interaction networks. Intrinsically disordered proteins lack higher order structure and have functional advantages, but their dysregulation can cause several diseases. All the significant proteins responsible for RA were identified. On the basis of the data obtained, highly disordered proteins were selected. Further, MSA was done to find the similarity among the highly disordered proteins and their functional partners. To determine the most relevant functional partner( s)/interacting protein(s) out of large network, three filters were introduced in the methodology. RESULTS: The two filtered proteins, IBSP and FGF2, have common functions and also play a vital role in the pathways of RA. Thus, gives an in-depth knowledge of molecular mechanisms involved in Rheumatoid Arthritis and targeted therapeutics. CONCLUSION: The network analysis of these proteins has been explored using Cytoscape, and the proteins with favourable values of graph centrality parameters such as IBSP and FGF2 are identified. Interesting functional cross talk such as bio mineralization, boneremodelling, angiogenesis, cell differentiation, etc., of SPP1 with IBSP and FGF2 is found, which throws light into the fact that these two proteins play a vital role in the pathways of RA.

Recent Advances in Nanomaterials of Group XIV Elements of Periodic Table in Breast Cancer Treatment.

Breast cancer is one of the most common malignancies and a leading cause of cancer-related mortality among women worldwide. The elements of group XIV in the periodic table exhibit a wide range of chemical manners. Recently, there have been remarkable developments in the field of nanobiomedical research, especially in the application of engineered nanomaterials in biomedical applications. In this review, we concentrate on the recent investigations on the antiproliferative effects of nanomaterials of the elements of group XIV in the periodic table on breast cancer cells. In this review, the data available on nanomaterials of group XIV for breast cancer treatment has been documented, providing a useful insight into tumor biology and nano-bio interactions to develop more effective nanotherapeutics for cancer patients.

Editorial to the Special Issue: "Synthesis of Organic Ligands and Their Metal Complexes in Medicinal Chemistry".

The field of medicinal (organic, bioinorganic, and coordination) chemistry as well as the interdisciplinary studies related to medicine is a rapidly developing area of study [...].

How Good are Bacteriophages as an Alternative Therapy to Mitigate Biofilms of Nosocomial Infections.

Bacteria survive on any surface through the generation of biofilms that provide a protective environment to grow as well as making them drug resistant. Extracellular polymeric matrix is a crucial component in biofilm formation. The presence of biofilms consisting of common opportunistic and nosocomial, drug-resistant pathogens has been reported on medical devices like catheters and prosthetics, leading to many complications. Several approaches are under investigation to combat drug-resistant bacteria. Deployment of bacteriophages is one of the promising approaches to invade biofilm that may expose bacteria to the conditions adverse for their growth. Penetration into these biofilms and their destruction by bacteriophages is brought about due to their small size and ability of their progeny to diffuse through the bacterial cell wall. The other mechanisms employed by phages to infect biofilms may include their relocation through water channels to embedded host cells, replication at local sites followed by infection to the neighboring cells and production of depolymerizing enzymes to decompose viscous biofilm matrix, etc. Various research groups are investigating intricacies involved in phage therapy to mitigate the bacterial infection and biofilm formation. Thus, bacteriophages represent a good control over different biofilms and further understanding of phage-biofilm interaction at molecular level may overcome the clinical challenges in phage therapy. The present review summarizes the comprehensive details on dynamic interaction of phages with bacterial biofilms and the role of phage-derived enzymes - endolysin and depolymerases in extenuating biofilms of clinical and medical concern. The methodology employed was an extensive literature search, using several keywords in important scientific databases, such as Scopus, Web of Science, PubMed, ScienceDirect, etc. The keywords were also used with Boolean operator "And". More than 250 relevant and recent articles were selected and reviewed to discuss the evidence-based data on the application of phage therapy with recent updates, and related potential challenges.