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Herein we describe the synthesis and rearrangement of 1,3-diamino-2,7-naphthyridines and 1-amino-3-oxo-2,7-naphthyridines. In the case of 1,3-diamino-2,7-naphthyridines, it was found that the rearrangement reaction was influenced by both the substituent at the 7th position of the 2,7-naphthyridine ring and by the nature of the cyclic amine at the 1st position. The influence was mainly steric. The reaction of 1-amino-3-oxo-2,7-naphthyridines with amines was studied for the first time. It was revealed that for these substrates, the rearrangement occurs faster and without any influence of the alkyl and cyclic amine groups. We also observed the nucleophilic addition of the amine to the carbonyl group of the rearranged product with the formation of a Schiff base. The calculation of the ESP charges on these substrates indicates a considerable increase in the positive charge on the cyano group that suffers the nucleophilic attack during the rearrangement process, possibly explaining its increased tendency to react and to have a higher reaction velocity. [ABSTRACT FROM AUTHOR]

Viruses utilize host cells at all stages of their life cycle, from the transcription of genes and translation of viral proteins to the release of viral copies. The human immune system counteracts viruses through a variety of complex mechanisms, including both innate and adaptive components. Viruses have an ability to evade different components of the immune system and affect them, leading to disruption. This review covers contemporary knowledge about the virus-induced complex interplay of molecular interactions, including regulation of transcription and translation in host cells resulting in the modulation of immune system functions. Thorough investigation of molecular mechanisms and signaling pathways that are involved in modulating of host immune response to viral infections can help to develop novel approaches for antiviral therapy. In this review, we consider new therapeutic approaches for antiviral treatment. Modern therapeutic strategies for the treatment and cure of human immunodeficiency virus (HIV) are considered in detail because HIV is a unique example of a virus that leads to host T lymphocyte deregulation and significant modulation of the host immune response. Furthermore, peculiarities of some promising novel agents for the treatment of various viral infections are described. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases caused by blood coagulation system disorders are one of the leading causes of morbidity and mortality in the world. Research shows that blood clotting factors are involved in these thrombotic processes. Among them, factor Xa occupies a key position in the blood coagulation cascade. Another coagulation factor, XIa, is also a promising target because its inhibition can suppress thrombosis with a limited contribution to normal hemostasis. In this regard, the development of dual inhibitors as new generation anticoagulants is an urgent problem. Here we report the synthesis and evaluation of novel potential dual inhibitors of coagulation factors Xa and XIa. Based on the principles of molecular design, we selected a series of compounds that combine in their structure fragments of pyrrolo[3,2,1-ij]quinolin-2-one and thiazole, connected through a hydrazine linker. The production of new hybrid molecules was carried out using a two-stage method. The reaction of 5,6-dihydropyrrolo[3,2,1-ij]quinoline-1,2-diones with thiosemicarbazide gave the corresponding hydrazinocarbothioamides. The reaction of the latter with DMAD led to the target methyl 2-(4-oxo-2-(2-(2-oxo-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1(2H)-ylidene)hydrazineyl)thiazol-5(4H)-ylidene)acetates in high yields. In vitro testing of the synthesized molecules revealed that ten of them showed high inhibition values for both the coagulation factors Xa and XIa, and the IC50 value for some compounds was also assessed. The resulting structures were also tested for their ability to inhibit thrombin. [ABSTRACT FROM AUTHOR]

Unlike most attempts to find compounds with activity against SARS-CoV-2 aimed at reusing approved drugs, our goal was to find compounds with antiviral activity among the 1,2-dithioloquinoline derivatives we synthesized. These compounds exhibit pleiotropic effects, having a novel structure compared to known pharmaceuticals. In this work, we diversified the structure of 1,2-dithioloquinoline by introducing various substituents (chlorine atom, ether, amide, sulfonamide groups, pharmacophore heterocycles) into different positions of this tricyclic framework. Using docking with further quantum chemical post-processing of calculations of the created virtual library of 404 structures, more than ten compounds of the aryl(4,4-dimethyl-4,5-dihydro-1H-[1,2]dithiolo[3,4-c]quinoline-1-ylidene)amine series were discovered, synthesized and experimentally studied. The bioactive screening of newly synthesized compounds revealed that six of them demonstrate suppression of SARS-CoV-2 replication in Vero E6 cell culture in the micromolar range of EC50 values (from 0.27 to 98.48 μM). The best compound, in the structure of which fragments of tricyclic dithioloquinoline and streptocide are combined, demonstrated a highest ability to protect Vero E6 cells from SARS-CoV-2 with EC50 = 0.27 μM, as well as low cytotoxicity with a selectivity index SI > 370, exceeding all reference values compounds used in the study (remdesivir, GC376, ML188). [ABSTRACT FROM AUTHOR]

HIV-1 remains a major health problem worldwide since the virus has developed drug-resistant strains, so, the need for novel agents is urgent. The protein reverse transcriptase plays fundamental role in the viruses' replication cycle. FDA approved Delavirdine bearing a sulfonamide moiety, while thiazolidinone has demonstrated significant anti-HIV activity as a core heterocycle or derivative of substituted heterocycles. In this study, thirty new thiazolidinone derivatives (series A, B and C) bearing sulfonamide group were designed, synthesized and evaluated for their HIV-1 RT inhibition activity predicted by computer program PASS taking into account the best features of available NNRTIs as well as against SARS-COV-2 main protease. Seven compounds showed good anti-HIV inhibitory activity, with two of them, C1 and C2 being better (IC 50 0.18 μΜ & 0.12 μΜ respectively) than the reference drug nevirapine (IC 50 0.31 μΜ). The evaluation of molecules to inhibit the main protease revealed that 6 of the synthesized compounds exhibited excellent to moderate activity with two of them (B4 and B10) having better IC 50 values (0.15 & 0.19 μΜ respectively) than the reference inhibitor GC376 (IC 50 0.439 μΜ). The docking studies is coincides with experimental results, showing good binding mode to both enzymes., (© 2024 The Author(s). Chemistry & Biodiversity published by Wiley-VHCA AG.)

Herein, we describe the synthesis of new hybrids linked to 1,2,3- and 1,2,4-triazole units. Hybrids connected to a 1,2,3-triazole ring were synthesized using the well-known click reaction. The synthesis of the 1,2,4-triazole-based hybrids was carried out using 2-[(4-cyano-1-methyl(2-furyl)-5,6,7,8-tetrahydroisoquinolin-3-yl)oxy]acetohydrazides as starting compounds. The compounds were evaluated for their anticonvulsive activity via antagonism towards pentylenetetrazole (PTZ) - and thiosemicarbazide (TSC)-induced convulsion and maximal electroshock-induced seizure (MES). Furthermore, the most active compounds were studied for their locomotory and anxiolytic activity via the "open field" and elevated plus maze (EPM) assays. Finally, their antidepressant activity was studied via the "forced swim" method. All the hybrids displayed pentylenetetrazole antagonism, ranging from 40% to 80%, while in the TSC model, the most active compounds increased latency of thiosemicarbazide seizures to 1.9-4.65 times compared to that of the control. Some of the tested compounds exhibited a pronounced anxiolytic and antidepressant effect. Docking study demonstrated complete agreement with experimental pharmacological data. It was revealed that the most active compounds have a pyrano[3,4- c ]pyridine ring in their structure., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)