Anti-inflammatory action of new hybrid N-acyl-[1,2]dithiolo-[3,4-c]quinoline-1-thione.

Most of pharmaceutical agents display a number of biological activities. It is obvious that testing even one compound for thousands of biological activities is not practically possible. A computer-aided prediction is therefore the method of choice in this case to select the most promising bioassays for particular compounds. Using the PASS Online software, we determined the probable anti-inflammatory action of the 12 new hybrid dithioloquinolinethiones derivatives. Chemical similarity search in the World-Wide Approved Drugs (WWAD) and DrugBank databases did not reveal close structural analogues with the anti-inflammatory action. Experimental testing of anti-inflammatory activity of the synthesized compounds in the carrageenan-induced inflammation mouse model confirmed the computational predictions. The anti-inflammatory activity of the studied compounds (2a, 3a-3k except for 3j) varied between 52.97% and 68.74%, being higher than the reference drug indomethacin (47%). The most active compounds appeared to be 3h (68.74%), 3k (66.91%) and 3b (63.74%) followed by 3e (61.50%). Thus, based on the in silico predictions a novel class of anti-inflammatory agents was discovered.

Functionally substituted 2-aminothiazoles as antimicrobial agents: in vitro and in silico evaluation.

Nine new functionally substituted derivatives of 2-aminothiazole were evaluated for antimicrobial activity using microdilution method against the panel of eight bacterial and eight fungal strains. Evaluation of antibacterial activity revealed that compounds are potent antibacterial agents, more active than ampicillin and streptomycin except of some compounds against B. cereus and En. cloacae. The best compound appeared to be compound 8. The most sensitive bacteria appeared to be En. cloacae, while L. monocytogenes was the most resistant. Compounds also exhibited good antifungal activity much better than two reference drugs, ketoconazole and bifonazole. Compound 1 exhibited the best antifungal activity. The most sensitive fungus was T. viride, while A. fumigatus was the most resistant. Bacteria as well as fungi in general showed different sensitivity towards compounds tested. Molecular docking studies revealed that MurB inhibition is probably involved in the mechanism of antibacterial activity, while CYP51 of C. albicans is responsible for the mechanism of antifungal activity. Finally, it should be mentioned that all compounds displayed very good druglikeness scores.

Imidazole Derivative As a Novel Translation Inhibitor.

Searching for novel compounds with antibiotic activity and understanding their mechanism of action is extremely important. The ribosome is one of the main targets for antibiotics in bacterial cells. Even if the molecule does not suit the clinical application for whatever reasons, an investigation of its mechanism of action can deepen our understanding of the ribosome function. Such data can inform us on how the already used translational inhibitors can be modified. In this study, we demonstrate that 1-(2-oxo-2-((4-phenoxyphenyl).

[A review on the monograph of N.R. Efimochkina «Bacterial food pathogens of the genus Campylobacter¼].

In the presented review of the book N.R. Efimochkina "Bacterial food pathogens of the Campylobacter genus" (Moscow, 2019) attention is drawn to the safety of food products and food raw materials, especially poultry products for consumers. In general, the problematic issues of campylobacteriosis and its causative agent are highlighted in a new way: the main reservoirs, sources and factors of pathogen transmission are indicated, theoretical issues are analyzed and generalized data of screening studies of food products and environmental objects in the poultry industry for bacteria of the genus Campylobacter are presented. Particular attention is paid to laboratory diagnostics of the pathogen for the presence of uncultivated forms of these pathogens, the existence of Campylobacter in biofilms, and the resistance of isolated cultures to antibiotics. Laboratory methods that improve the detection of these pathogens are proposed. The developed methodological documents that accelerate the processes of Campylobacter isolation and antibiotic resistance assessment are relevant, which is important for the efficiency of production control and sanitary inspections of poultry and meat processing enterprises at control critical points. The introduction of the methods described in the monograph for analyzing the content of Campylobacter in food products, on the surface of equipment and inventory will help to effectively manage the risks associated with contamination of food products by these pathogens. The monograph will be of great importance for improving the knowledge of a number of medical staff, including sanitary and hygienic profile, that is important for environmental protection, the prevention of food poisoning and intestinal infections with alimentary transmission factor.

Antibacterial activity of griseofulvin analogues as an example of drug repurposing.

Griseofulvin is a well-known antifungal drug that was launched in 1962 by Merck & Co. for the treatment of dermatophyte infections. However, according to predictions using the Way2Drug computational drug repurposing platform, it may also have antibacterial activity. As no confirmation of this prediction was found in the published literature, this study estimated in-silico antibacterial activity for 42 griseofulvin derivatives. Antibacterial activity was predicted for 33 of the 42 compounds, which led to the conclusion that this activity might be considered as typical for this chemical series. Therefore, experimental testing of antibacterial activity was performed on a panel of Gram-positive and Gram-negative micro-organisms. Antibacterial activity was evaluated using the microdilution method detecting the minimal inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC). The tested compounds exhibited potent antibacterial activity against all the studied bacteria, with MIC and MBC values ranging from 0.0037 to 0.04 mg/mL and from 0.01 to 0.16 mg/mL, respectively. Activity was 2.5-12 times greater than that of ampicillin and 2-8 times greater than that of streptomycin, which were used as the reference drugs. Similarity analysis for all 42 compounds with the (approximately) 470,000 drug-like compounds indexed in the Clarivate Analytics Integrity database confirmed the significant novelty of the antibacterial activity for the compounds from this chemical class. Therefore, this study demonstrated that by using computer-aided prediction of biological activity spectra for a particular chemical series, it is possible to identify typical biological activities which may be used for discovery of new applications (e.g. drug repurposing).

Molecular docking, design, synthesis and biological evaluation of novel 2,3-aryl-thiazolidin-4-ones as potent NNRTIs.

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) remain the most promising anti-AIDS agents that target the HIV-1 reverse transcriptase enzyme (RT). However, the efficiency of approved NNRTI drugs has decreased by the appearance of drug-resistant viruses and side effects upon long-term usage. Thus, there is an urgent need for developing new, potent NNRTIs with broad spectrum against HIV-1 virus and with improved properties. In this study, a series of thiazolidinone derivatives was designed based on a butterfly mimicking scaffold consisting of a substituted benzothiazolyl moiety connected with a substituted phenyl ring via a thiazolidinone moiety. The most promising derivatives were selected using molecular docking analysis and PASS prediction program, synthesized and evaluated for HIV-1 RT inhibition. Five out of fifteen tested compounds exhibited good inhibitory action. It was observed that the presence of Cl or CN substituents at the position 6 of the benzothiazole ring in combination with two fluoro atoms at the ortho-positions or a hydrogen acceptor substituent at the 4-position of the phenyl ring are favourable for the HIV RT inhibitory activity.

Appendix A. dithioloquinolinethiones as new potential multitargeted antibacterial and antifungal agents: Synthesis, biological evaluation and molecular docking studies.

Herein we report the design, synthesis, molecular docking study and evaluation of antimicrobial activity of ten new dithioloquinolinethiones. The structures of compounds were confirmed by 1H NMR, 13C NMR and HPLC-HRMS. Before evaluation of their possible antimicrobial activity prediction of toxicity was performed. All compounds showed antibacterial activity against eight Gram positive and Gram negative bacterial species. All compounds appeared to be more active than ampicillin and almost all than streptomycin. The best antibacterial activity was observed for compound 8c 4,4,8-trimethyl-5-{[(4-phenyl-5-thioxo-4,5-dihydro-1,3,4-thiadiazol-2-yl)thio]acetyl}-4,5-dihydro-1H-[1,2]dithiolo[3,4c]quino lone-1-thione). The most sensitive bacterium En.cloacae followed by S. aureus, while L.monocytogenes was the most resistant. All compounds were tested for antifungal activity also against eight fungal species. The best activity was expressed by compound 8d (5-[(4,5-Dihydro-1,3-thiazol-2-ylthio)acetyl]-4,4-dimethyl-4,5-dihydro-1H-[1,2]dithiolo[3,4-c]quinoline-1-thione). The most sensitive fungal was T. viride, while P. verrucosum var. cyclopium was the most resistant one. All compounds were more potent as antifungal agent than reference compound bifonazole and ketoconazole. The docking studies indicated a probable involvement of E. coli DNA GyrB inhibition in the anti-bacterial mechanism, while CYP51ca inhibition is probably responsible for antifungal activity of tested compounds. It is interesting to mention that docking results coincides with experimental.

Phenoptosis in arthropods and immortality of social insects.

In general, there are no drastic differences in phenoptosis patterns in plant and animal organisms. However, there are some specific features characteristic for insects and other arthropods: 1) their development includes metamorphosis with different biochemical laws at consecutive developmental stages; 2) arthropods can reduce or stop development and aging when in a state of diapause or temporal cold immobility; 3) their life cycle often correlates with seasonal changes of surroundings; 4) polymorphism is widespread - conspecifics differ by their lifespans and phenoptosis features; 5) lifespan-related sexual dimorphism is common; 6) significant situational plasticity of life cycle organization is an important feature; for example, the German wasp (Paravespula germanica) is obligatorily univoltine in the temperate zone, while in tropical regions its lifespan increases and leads to repeated reproduction; 7) life cycles of closely related species may differ significantly, for example, in contrast to German wasp, some tropical hornets (Vespa) have only one reproduction period. Surprisingly, many insect species have been shown to be subjected to gradual aging and phenoptosis, like the highest mammals. However, queens of social insects and some long-lived arachnids can apparently be considered non-aging organisms. In some species, lifespan is limited to one season, while others live much longer or shorter. Cases of one-time reproduction are rather rare. Aphagia is common in insects (over 10,000 species). Cannibalism is an important mortality factor in insects as well as in spiders. In social insects, which exist only in colonies (families), the lifetime of a colony can be virtually unlimited. However, in case of some species the developmental cycle and death of a colony after its completion are predetermined. Most likely, natural selection in insects does not lengthen individual lifespan, but favors increase in reproduction efficiency based on fast succession of generations leading to increased evolvability.

[The mechanisms of the inhibition of erythrocyte acetylcholinesterase activity by photodynamic herbicides]. / Mekhanizmy tormozheniia aktivnosti éritrotsitarnoi atsetilkholinésterazy nekotorymi fotodinamicheskimi gerbitsidami.

A comparative study of kinetics and mechanisms of action of some photodynamic herbicides (dipyridil, phenantroline, and acepox) on mechanical resistance and acetylcholinesterase activity of erythrocytes has been carried out. Acepox had a slight damaging effect, and phenantroline was the strongest inhibitor. The data on mechanical destruction of erythrocytes correlated with tests on toxicity of obtained samples carried out on mice and infusorians. The proposed criteria may help to search for nontoxic drugs.

[Human visual functions during mild vestibular exposures]. / Zritel'nye funktsii cheloveka pri slabykh vestibuliarnykh vozdeistviiakh.

Human experiments have shown that after mild stimulation of semi-circular receptors, which induces no motion sickness symptoms, the time of recovery of the central vision acuity shortens and after stimulation of otolith receptors tends to increase. Thresholds of color discrimination as applied to the red, green and violet colours as well as the course of back adaptation after mild stimulation of otolith receptors remain unchanged. The time of appearance of the Purkinje phenomenon after stimulation of receptors of semi-circular canals often remains unaltered and sometimes increases. It is assumed that the visual fixation of objects occurring with the time deficiency as related to the object display is accompanied by a compensatory-adaptive increase in the resolution capacity of the visual system.

[Recovery of central vision after temporary blindness]. / Nekotorye zakonomernosti vosstanovleniia tsentral'nogo zreniia posle vremennogo oslepleniia

Recovery of spatial resolving capacity (acuity) of central vision after temporary blindness induced by prolonged (1.5, 3, 6 min) light adaptation to a sun or incandescence lamp (20, 40, 80 thous. lux) illuminated white screen was studied. The recovery time increased exponentially with an increase in energy light stimulation (product of brightness of the deadapting source by the time of action). A general formula describing the relationship between the time of recovery of acuity and brightness of the test table and energy of light stimulus was derived.