New Thiosemicarbazide Derivatives with Multidirectional Biological Action.

Over the years, several new medicinal substances have been introduced for the treatment of diseases caused by bacteria and parasites. Unfortunately, due to the production of numerous defense mechanisms by microorganisms and parasites, they still pose a serious threat to humanity around the world. Therefore, laboratories all over the world are still working on finding new, effective methods of pharmacotherapy. This research work aimed to synthesize new compounds derived from 3-trifluoromethylbenzoic acid hydrazide and to determine their biological activity. The first stage of the research was to obtain seven new compounds, including six linear compounds and one derivative of 1,2,4-triazole. The PASS software was used to estimate the potential probabilities of biological activity of the newly obtained derivatives. Next, studies were carried out to determine the nematocidal potential of the compounds with the use of nematodes of the genus Rhabditis sp. and antibacterial activity using the ACCT standard strains. To determine the lack of cytotoxicity, tests were performed on two cell lines. Additionally, an antioxidant activity test was performed due to the importance of scavenging free radicals in infections with pathogenic microorganisms. The conducted research proved the anthelmintic and antibacterial potential of the newly obtained compounds. The most effective were two compounds with a 3-chlorophenyl substituent, both linear and cyclic derivatives. They demonstrated higher efficacy than the drugs used in treatment.

Design and Synthesis of Menthol and Thymol Derived Ciprofloxacin: Influence of Structural Modifications on the Antibacterial Activity and Anticancer Properties.

Sixteen new Ciprofloxacin derivatives were designed and successfully synthesized. In an in silico experiment, lipophilicity was established for obtained compounds. All compounds were screened for antimicrobial activity using standard and clinical strains. As for Gram-positive hospital microorganisms, all tested derivatives were active. Measured MICs were in the range 1-16 µg/mL, confirming high antimicrobial potency. Derivative 12 demonstrated activity against all standard Gram-positive Staphylococci, within the range of 0.8-1.6 µg/mL and was confirmed as the leading structure with MICs 1 µg/mL for S. pasteuri KR 4358 and S. aureus T 5591 (clinical strains). All compounds were screened for their in vitro cytotoxic properties via the MTT method. Three of the examined compounds (3, 11 and 16) showed good activity against cancer cells, and in parallel were found not to be cytotoxic toward normal cells. Doxorubicin SI ranged 0.14-1.11 while the mentioned three ranged 1.9-3.4. Selected Ciprofloxacin derivatives were docked into the crystal structure of topoisomerase II (DNA gyrase) in complex with DNA (PDB ID: 5BTC). In summary, leading structures were established (3, 11, 12 and 16). We have observed poor results in preformed studies for disubstituted derivatives, suggesting that 3-oxo-4-carboxylic acid core is the active DNA-gyrase binding site, and when structural changes were made in this fragment, there was an observed decrease in antibacterial potency.