The most common etiological factors of conjunctivitis

Conjunctivitis is one of the most common diseases of the anterior segment. It is characterized by redness of the eye, conjunctivital injection, the presence of secretions in the conjunctival sac. The most common symptoms reported by patients include: pain, redness, itching, foreign body sensation and photophobia. Intensifying severe symptoms can lead to difficulties in daily activities. The correct diagnosis of the etiological agent is essential to implement an appropriate treatment and relieve symptoms of the disease

Multidirectional Efficacy of Biologically Active Nitro Compounds Included in Medicines

The current concept in searching for new bioactive products, including mainly original active substances with potential application in pharmacy and medicine, is based on compounds with a previously determined structure, well-known properties, and biological activity profile. Nowadays, many commonly used drugs originated from natural sources. Moreover, some natural materials have become the source of leading structures for processing further chemical modifications. Many organic compounds with great therapeutic significance have the nitro group in their structure. Very often, nitro compounds are active substances in many well-known preparations belonging to different groups of medicines that are classified according to their pharmacological potencies. Moreover, the nitro group is part of the chemical structure of veterinary drugs. In this review, we describe many bioactive substances with the nitro group, divided into ten categories, including substances with exciting activity and that are currently undergoing clinical trials

Multidirectional Efficacy of Biologically Active Nitro Compounds Included in Medicines

The current concept in searching for new bioactive products, including mainly original active substances with potential application in pharmacy and medicine, is based on compounds with a previously determined structure, well-known properties, and biological activity profile. Nowadays, many commonly used drugs originated from natural sources. Moreover, some natural materials have become the source of leading structures for processing further chemical modifications. Many organic compounds with great therapeutic significance have the nitro group in their structure. Very often, nitro compounds are active substances in many well-known preparations belonging to different groups of medicines that are classified according to their pharmacological potencies. Moreover, the nitro group is part of the chemical structure of veterinary drugs. In this review, we describe many bioactive substances with the nitro group, divided into ten categories, including substances with exciting activity and that are currently undergoing clinical trials

Microwave (MW), Ultrasound (US) and Combined Synergic MW-US Strategies for Rapid Functionalization of Pharmaceutical Use Phenols

Increasingly stringent regulations aimed at protection of the natural environment have stimulated the search for new synthetic methodologies in organic and medicinal chemistry having no or minimum harmful effect. An interesting approach is the use of alternative activation factors, microwaves (MW) or ultrasounds (US) and also their cross-combination, which has been tested in the fast and efficient creation of new structures. At present, an easy and green hybrid strategy (“Lego” chemistry) is generally recommended for the design of new substances from different chemistry building blocks. Often, selected biologically active components with specific chemical reactivities are integrated by a suitably designed homo- or heterodifunctional linker that modifies the functionality of the starting structure, allowing easy covalent linkage to another molecule. In this study, a fast introduction of heterodifunctional halogenoacidic linker to selected mono-, di- and triphenolic active substances, allowing their functionalization, was investigated. Nucleophilic substitution reaction was chosen to produce final ethers with the reactive carboxylic group from phenols. The functionalization was performed using various green factors initiating and supporting the chemical reactions (MW, US, MW-US). The benefits of the three green supporting methods and different conditions of reactions were analyzed and compared with the results of the reaction performed by conventional methods

Hybrid Compounds Strategy in the Synthesis of Oleanolic Acid Skeleton-NSAID Derivatives

The current study focuses on the synthesis of several hybrid individuals combining a natural oleanolic acid skeleton and synthetic nonsteroidal anti-inflammatory drug moieties (NSAIDs). It studied structural modifications of the oleanolic acid structure by use of the direct reactivity of hydroxyl or hydroxyimino groups at position C-3 of the triterpenoid skeleton with the carboxylic function of anti-inflammatory drugs leading to new perspective compounds with high potential pharmacological activities. Novel ester- and iminoester-type derivatives of oleanolic unit with the different NSAIDs, such as ibuprofen, aspirin, naproxen, and ketoprofen, were obtained and characterized. Moreover, preliminary research of compounds obtaining structure stability under acidic conditions was examined and the PASS method of prediction of activity spectra for substances was used to estimate the potential biological activity of these compounds

Molecular Consortia—Various Structural and Synthetic Concepts for More Effective Therapeutics Synthesis

The design and discovery of novel drug candidates are the initial and most probably the crucial steps in the drug development process. One of the tasks of medicinal chemistry is to produce new molecules that have a desired biological effect. However, even today the search for new pharmaceuticals is a very complicated process that is hard to rationalize. Literature provides many scientific reports on future prospects of design of potentially useful drugs. Many trends have been proposed for the design of new drugs containing different structures (dimers, heterodimers, heteromers, adducts, associates, complexes, biooligomers, dendrimers, dual-, bivalent-, multifunction drugs and codrugs, identical or non-identical twin drugs, mixed or combo drugs, supramolecular particles and various nanoindividuals. Recently much attention has been paid to different strategies of molecular hybridization. In this paper, various molecular combinations were described e.g., drug–drug or drug-non-drug combinations which are expressed in a schematic multi-factor form called a molecular matrix, consisting of four factors: association mode, connection method, and the number of elements and linkers. One of the most popular trends is to create small–small molecule combinations such as different hybrids, codrugs, drug–drug conjugates (DDCs) and small-large molecule combinations such as antibody-drug conjugates (ADCs), polymer-drug conjugates (PDCs) or different prodrugs and macromolecular therapeutics. A review of the structural possibilities of active framework combinations indicates that a wide range of potentially effective novel-type compounds can be formed. What is particularly important is that new therapeutics can be obtained in fast, efficient, and selective methods using current trends in chemical synthesis and the design of drugs such as the “Lego” concept or rational green approach

Charakterystyka izolatów Staphylococcus epidermidis wyhodowanych od pacjentów z zakażeniami endoprotez stawu biodrowego

Background. Coagulase negative staphylococci are at the forefront of etiologic agents of periprosthetic joint infections (PJIs). The purpose of the study was to characterise causative isolates (n=19) of Staphylococcus epidermidis (SE) – with emphasis on their phenotypic and genotypic heterogeneity. Material and methods. The isolates were cultured from multiple samples obtained perioperatively during revision surgery from 14 patients with clinically and/or microbiologically proven PJI. Phenotypic heterogeneity included variations of colony morphologies, drug resistance patterns and/or the capability of the biofilm formation and was verified by the DNA fingerprinting assay. Results. Phenotypic discrepancies were observed between isolates cultured from 5 patients (35.7%). The genotyping assay identified 3 pairs of isolates as unrelated; single pairs were genetically related and indistinguishable. The biofilm production was detected in 17 isolates, among which 5 (29.4%) were proficient biofilm formers harbouring the icaADBC genes. Additionally, one ica-positive isolate produced a moderate, protease-sensitive biofilm. The remaining isolates were moderate biofilm producers among which four developed protease-sensitive biofilms. Conclusions. The majority of PJIs are monoclonal; nevertheless, phenotypic diversity of SE is a frequent phenomenon which can complicate the diagnostic proceeding. Adherence ability is an important pathogenic trait of SE although the chemical composition of the resultant biofilm, its intensity and regulation of development can vary.Wprowadzenie. Gronkowce koagulazo-ujemne są wiodącymi czynnikami etiologicznymi zakażeń okołoprotezowych. Celem pracy była charakterystyka izolatów (n=19) Staphylococcus epidermidis (SE) ze szczególnym uwzględnieniem ich fenotypowej i genotypowej heterogenności. Materiał i metody. Izolaty gronkowców zostały wyhodowane z materiałów klinicznych pobranych śródoperacyjnie od 14 pacjentów, u których zakażenie endoprotezy stawu biodrowego zostało potwierdzone klinicznie i/lub mikrobiologicznie. Fenotypową heterogenność definiowano w oparciu o odmienne cechy morfologii kolonii bakteryjnych, profile lekowrażliwości izolatów i/lub ich zdolność tworzenia biofilmu w warunkach in vitro i weryfikowano ją na postawie genotypowania. Wyniki. Fenotypowe rozbieżności zaobserwowano pomiędzy izolatami SE wyhodowanymi od 5 (35.7%) pacjentów. W oparciu o wyniki genotypowania za genetycznie niespokrewnione uznano 3 pary izolatów, pojedyncze pary zaś za spokrewnione i nieodróżnialne/klonalne. Wytwarzanie biofilmu zostało potwierdzone dla 17 badanych izolatów, wśród których 5 (29.4%) wytwarzało intensywny biofilm i posiadało geny icaADBC. Ponadto, jeden izolat SE ica+ wytwarzał umiarkowany, wrażliwy na działanie proteazy biofilm. Pozostałe izolaty wytwarzały biofilm umiarkowany. Cztery z nich charakteryzowały się tworzeniem biofilmu wrażliwego na działanie proteazy. Wnioski. Większość PJIs ma charakter monoklonalny, niemniej jednak zmienność fenotypowa SE pozostaje częstym zjawiskiem, co może utrudniać diagnostykę zakażeń wywoływanych przez te drobnoustroje. Zdolność adherencji jest ważną cechą warunkującą patogenność SE, aczkolwiek skład chemiczny powstającego w jej wyniku biofilmu oraz jego intensywność i regulacja mechanizmów wpływających na jego tworzenie mogą różnić się pomiędzy izolatami

Synthesis, Cytotoxicity and Molecular Docking of New Hybrid Compounds by Combination of Curcumin with Oleanolic Acid

Curcumin and oleanolic acid are natural compounds with high potential in medicinal chemistry. These products have been widely studied for their pharmacological properties and have been structurally modified to improve their bioavailability and therapeutic value. In the present study, we discuss how these compounds are utilized to develop bioactive hybrid compounds that are intended to target cancer cells. Using a bifunctional linker, succinic acid, to combine curcumin and triterpenoic oleanolic acid, several hybrid compounds were prepared. Their cytotoxicity against different cancer cell lines was evaluated and compared with the activity of curcumin (the IC50 value (24 h), for MCF7, HeLaWT and HT-29 cancer cells for KS5, KS6 and KS8 compounds was in the range of 20.6–94.4 µM, in comparison to curcumin 15.6–57.2 µM). Additionally, in silico studies were also performed. The computations determined the activity of the tested compounds towards proteins selected due to their similar binding modes and the nature of hydrogen bonds formed within the cavity of ligand−protein complexes. Overall, the curcumin-triterpene hybrids represent an important class of compounds for the development of effective anticancer agents also without the diketone moiety in the curcumin molecule. Moreover, some structural modifications in keto-enol moiety have led to obtaining more information about different chemical and biological activities. Results obtained may be of interest for further research into combinations of curcumin and oleanolic acid derivatives