Determination of the Lipophilicity of Some New Derivatives of Thiosemicarbazide and 1,2,4-triazoline-5-thione with Potential Antituberculosis Activity

The chromatographic behavior of newly obtained derivatives of thiosemicarbazide and 1,2,4- triazoline-5-thione was determined. The lipophilicity was confirmed by the use of the Reversed Phase Thin-Layer Chromatography (RP-TLC) method. For both groups of solutes the lipophilicity depended on the substituents. All obtained compounds were tested for their antimycotic activity. The strongest antituberculosis activity was observed for 4-(2-iodophenyl)-1-(pyridine-4-ylacetyl)thiosemicarbazide 4 and 4- phenyl-3-(pyridine-4-ylmethyl)-1,2,4-triazoline-5-thione 27

Determination of the Lipophilicity of Some New Derivatives of Thiosemicarbazide and 1,2,4-triazoline-5-thione with Potential Antituberculosis Activity

The chromatographic behavior of newly obtained derivatives of thiosemicarbazide and 1,2,4- triazoline-5-thione was determined. The lipophilicity was confirmed by the use of the Reversed Phase Thin-Layer Chromatography (RP-TLC) method. For both groups of solutes the lipophilicity depended on the substituents. All obtained compounds were tested for their antimycotic activity. The strongest antituberculosis activity was observed for 4-(2-iodophenyl)-1-(pyridine-4-ylacetyl)thiosemicarbazide 4 and 4- phenyl-3-(pyridine-4-ylmethyl)-1,2,4-triazoline-5-thione 27

The Effect of Combining Natural Terpenes and Antituberculous Agents against Reference and Clinical Mycobacterium tuberculosis Strains

Background: On account of emergence of multi- and extensively drug-resistant Mycobacterium tuberculosis (Mtb) strains, combinations of drugs with natural compounds were tested to search for antibiotic activity enhancers. In this work we studied terpenes (α-pinene, bisabolol, β-elemene, (R)-limonene, (S)-limonene, myrcene, sabinene), which are the main constituents of essential oil obtained from Mutellina purpurea L., a plant with described antitubercular activity, to investigate their interactions with antibiotics against reference Mtb strains and multidrug-resistant clinical isolates. Methods: The serial dilution method was used to evaluate the minimal inhibitory concentration (MIC) of tested compounds, while the fractional inhibitory concentration index (FICI) was calculated for characterization of interactions. Moreover, IC50 values of tested compounds were determined using monkey kidney epithelial cell line (GMK). Results: The combinations of all studied terpenes with ethambutol or rifampicin resulted in a synergistic interaction. Bisabolol and (R)-limonene decreased the MIC for rifampicin at least two-fold for all tested strains, however no synergistic action was observed against virulent strains. The tested terpenes showed slight (bisabolol) or no cytotoxic effect against normal eukaryotic cells in vitro. Conclusions: The obtained enhanced activity (FICI < 0.5) of ethambutol and rifampicin against H37Ra strain under the influence of the studied terpenes may be correlated to the capability of essential oil constituents to modify bacterial resistance mechanisms in general. The observed differences in avirulent and virulent bacteria susceptibility to terpenes tested separately and in combinations with antibiotics can be correlated with the differences in the cell wall structure between H37Ra mutant and all virulent strains

Nigella damascena L. Essential Oil—A Valuable Source of β-Elemene for Antimicrobial Testing

The most commonly used plant source of β-elemene is Curcuma wenyujin Y. H. Chen & C. Ling (syn. of Curcuma aromatic Salisb.) with its content in supercritical CO2 extract up to 27.83%. However, the other rich source of this compound is Nigella damascena L. essential oil, in which β-elemene accounts for 47%. In this work, the effective protocol for preparative isolation of β-elemene from a new source—N. damascena essential oil—using high performance counter-current chromatography HPCCC was elaborated. Furthermore, since sesquiterpens are known as potent antimicrobials, the need for finding new agents designed to combat multi-drug resistant strains was addressed and the purified target compound and the essential oil were tested for its activity against a panel of Gram-positive and Gram-negative bacteria, fungi, and mycobacterial strains. The application of the mixture of petroleum ether, acetonitrile, and acetone in the ratio 2:1.5:0.5 (v/v) in the reversed phase mode yielded β-elemene with high purity in 70 min. The results obtained for antimicrobial assay clearly indicated that N. damascena essential oil and isolated β-elemene exert action against Mycobacterium tuberculosis strain H37Ra

New Application of 1,2,4-Triazole Derivatives as Antitubercular Agents. Structure, In Vitro Screening and Docking Studies

A series of 1,2,4-triazole derivatives were synthesized and assigned as potential anti-tuberculosis substances. The molecular and crystal structures for the model compounds C1, C12, and C13 were determined using X-ray analysis. The X-ray investigation confirmed the synthesis pathway and the assumed molecular structures for analyzed 1,2,4-triazol-5-thione derivatives. The conformational preferences resulting from rotational degrees of freedom of the 1,2,4-triazole ring substituents were characterized. The lipophilicity (logP) and electronic parameters as the energy of frontier orbitals, dipole moments, NBO net charge distribution on the atoms, and electrostatic potential distribution for all structures were calculated at AM1 and DFT/B3LYP/6-311++G(d,p) level. The in vitro test was done against M. tuberculosis H37Ra, M. phlei, M. smegmatis, and M. timereck. The obtained results clearly confirmed the antituberculosis potential of compound C4, which turned out to be the most active against Mycobacterium H37Ra (MIC = 0.976 μg/mL), Mycobaterium pheli (MIC = 7.81 μg/mL) and Mycobacerium timereck (62.6 μg/mL). Satisfactory results were obtained with compounds C8, C11, C14 versus Myc. H37Ra, Myc. pheli, Myc. timereck (MIC = 31.25−62.5 μg/mL). The molecular docking studies were carried out for all investigated compounds using the Mycobacterium tuberculosis cytochrome P450 CYP121 enzyme as molecular a target connected with antimycobacterial activity