The processes used by academic and industrial scientists to discover new drugs have recently experienced a true renaissance, with many new and exciting techniques being developed over the past 5–10 years alone. Drug design and discovery, and the search for new safe and well-tolerated compounds, as well as the ineffectiveness of existing therapies, and society’s insufficient knowledge concerning the prophylactics and pharmacotherapy of the most common diseases today, comprise a serious challenge. This can influence not only the quality of human life, but also the health of whole societies, which became evident during the COVID-19 pandemic. In general, the process of drug development consists of three main stages: drug discovery, preclinical development using cell-based and animal models/tests, clinical trials on humans and, finally, forward moving toward the step of obtaining regulatory approval, in order to market the potential drug. In this review, we will attempt to outline the first three most important consecutive phases in drug design and development, based on the experience of three cooperating and complementary academic centers of the Visegrád group; i.e., Medical University of Lublin, Poland, Masaryk University of Brno, Czech Republic, and Comenius University Bratislava, Slovak Republic.

Koronav?rus 2 vyvol?vaj?ci ?a?k? ak?tny respira?n? syndr?m (SARS-CoV-2) a pand?mia ochorenia COVID-19 (COrona VIrus Disease-19), ktor? je t?mto v?rusom zapr??inen?, v priebehu polroka zmenili svet. Deficit efekt?vnej terapie COVID-19, spolu s ... Koronav?rus 2 vyvol?vaj?ci ?a?k? ak?tny respira?n? syndr?m (SARS-CoV-2) a pand?mia ochorenia COVID-19 (COrona VIrus Disease-19), ktor? je t?mto v?rusom zapr??inen?, v priebehu polroka zmenili svet. Deficit efekt?vnej terapie COVID-19, spolu s ...

The micellization process of the local anaesthetic carbisocainium chloride in water was investigated by two spectral methods using the probe pyrene. First, the absorption spectroscopy in UV/VIS region was based on studying changes in characteristic absorption spectrum of pyrene in presence of surfactant. The resultant plot of the sum of absorbances for all the major pyrene peaks as a function of the total surfactant concentration shows, around the critical micellar concentration, a typical sigmoidal increase. The fluorescence emission spectroscopy in UV/VIS region of spectrum by the probe pyrene, second procedure, was applied for determination of the cmc from the measurements of the pyrene I₁ /I₃ ratio as a function of the surfactant concentration. The pyrene ratio data were fitted by the Boltzmann-type sigmoid of decreasing character.

This research focused on a three-step synthesis, analytical, physicochemical, and biological evaluation of hybrid molecules 6a–g, containing a lipophilic 3-trifluoromethylphenyl moiety, polar carbamoyloxy bridge, 2-hydroxypropan-1,3-diyl chain and 4-(substituted phenyl)-/4-diphenylmethylpiperazin-1-ium-1-yl fragment. The estimation of analytical and physicochemical descriptors (m/z_measured via HPLC-UV/HR-MS, log ε_{2 (Ch–T)} from UV/Vis spectrophotometry and log k_w via RP-HPLC) as well as in vitro antimycobacterial and cytotoxic screening of given compounds were carried out (i.e., determination of MIC and IC₅₀ values). These highly lipophilic molecules (log k_w = 4.1170–5.2184) were tested against Mycobacterium tuberculosis H₃₇R_a ATCC 25177 (Mtb H₃₇R_a), M. kansasii DSM 44162 (MK), M. smegmatis ATCC 700084 (MS), and M. marinum CAMP 5644 (MM). The impact of the 6a–g set on the viability of human liver hepatocellular carcinoma (HepG2) cells was also investigated. 1-[2-Hydroxypropyl-{(3-trifluoromethyl)- phenyl}carbamoyloxy]-4-(3,4-dichlorophenyl)piperazin-1-ium chloride (6e) and 1-[2-hydroxy- propyl-{(3-trifluoromethyl)phenyl}carbamoyloxy]-4-(4-diphenylmethyl)piperazin-1-ium chloride (6g) most effectively inhibited the growth of Mtb H₃₇R_a (MIC < 3.80 μM). The substance 6g also showed interesting activity against MM (MIC = 8.09 μM). All obtained data served as input values for structure-activity relationship evaluations using statistical principal component analysis. In fact, the toxicity of both 6e (IC₅₀ = 29.39 μM) and 6g (IC₅₀ = 22.18 μM) in HepG2 cells as well as selectivity index (SI) values (SI < 10.00) prevented to consider these promising antimycobacterials safe.