Synthesis, Crystal Structures, Lipophilic Properties and Antimicrobial Activity of 5-Pyridylmethylidene-3-rhodanine-carboxyalkyl Acids Derivatives

Abstract

The constant increase in the resistance of pathogenic bacteria to the commonly used drugs so far makes it necessary to search for new substances with antibacterial activity. Taking up this challenge, we obtained a series of rhodanine-3-carboxyalkyl acid derivatives containing 2- or 3- or 4-pyridinyl moiety at the C-5 position. These compounds were tested for their antibacterial and antifungal activities. They showed activity against Gram-positive bacteria while they were inactive against Gram-negative bacteria and yeast. In order to explain the relationship between the activity of the compounds and their structure, for selected derivatives crystal structures were determined using the X-ray diffraction method. Modeling of the isosurface of electron density was also performed. For all tested compounds their lipophilicity was determined by the RP-TLC method and by calculation methods. On the basis of the carried-out research, it was found that the derivatives with 1.5 N···S electrostatics interactions between the nitrogen atom in the pyridine moiety and the sulfur atom in the rhodanine system showed the highest biological activity.

Architecture of the rings of 5-arylidenerhodanine derivatives versus P-gp inhibition

“…The interplanar angles ( � ) between the planes containing rings in investigated compounds 1-5 and other derivatives with crystal structures determined earlier, i.e. 6-9 (Z ˙esławska et al, 2022b;Smith et al, 2009). 2 A:13.9 (2) A:47.6 (1) -A:60.1 (2) --B:44.2 (1) B:44.2 (1) -B:60.9 (2) -- 3* 1.42 (6) 89.2 (1) -89.5 (1) --4 24.5 (1) 2.4 (1) -22.7 (1) --5* D:7.3 (2) D:64.9 (1) D:55.2 (1) D:61.1 (1) D:61.9 (1) D:77.0 (1) E:13.2 (1) E:62.2 (1) E:76.2 (1) E:65.9 (1) E:63.6 (1) E:81.1 (1) 6 D:18.1 (1) D:42.27 (7) ring(s) seems to have an influence on biological activity.…”

“…The family of rhodanine derivatives is of interest in medicinal chemistry because of their various biological actions, for example, antibacterial (Maddila et al, 2020;Tejchman et al, 2020;Z ˙esławska et al, 2022a), antifungal (Chauhan et al, 2012), antiparasitic (Tejchman et al, 2022), anticancer (Yin et al, 2022), antidiabetic (Andleeb et al, 2016) and antiviral (Lesyk, 2020). Recently, 5-arylidenerhodanine derivatives have been studied as potential modulators of the MDR efflux pump P-gp (Z ˙esławska et al, 2022b).…”

“…Therefore, both the crystal structures of proteins with inhibitors and the crystal structures of small molecules able to inhibit P-gp, as well as molecular modelling studies, provide valuable information on the structural features of compounds which will aid in the search for new compounds with better activity. In recent years, it has been found that hydrophobic interactions are mainly responsible for the binding of compounds to P-gp, but the impact of hydrogen bonding cannot be ignored (Mollazadeh et al 2018;Seelig, 2020;Z ˙esławska et al, 2021, 2022b.…”

Simultaneous effect of different chromatographic conditions on the chromatographic retention of pentapeptide derivatives (HGRFG and NPNPT)

“…The coefficient of the Soczewiński–Wachtmeister equation is related to not only the length of the alkyl chain in the molecule but also the latitude of the mobile phase composition ( Żesławska et al, 2022 ). Generally, a wider range of methanol concentrations correlates with more accurate coefficients.…”

Can a Small Change in the Heterocyclic Substituent Significantly Impact the Physicochemical and Biological Properties of (Z)-2-(5-Benzylidene-4-oxo-2-thioxothiazolidin-3-yl)acetic Acid Derivatives?

“…This is primarily due to the growing requirements placed on chemical compounds used, among others, in technology, pharmacy and medicine. In recent years, derivatives of rhodanine-3-acetic acid have become increasingly popular in scientific research [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. These compounds exhibit many interesting physicochemical and biological properties, so they are being investigated for numerous applications [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ].…”