Pharmacological and Structure-Activity Relationship Evaluation of 4-aryl-1-Diphenylacetyl(thio)semicarbazides

This article describes the synthesis of six 4-aryl-(thio)semicarbazides (series a and b) linked with diphenylacetyl moiety along with their pharmacological evaluation on the central nervous system in mice and computational studies, including conformational analysis and electrostatic properties. All thiosemicarbazides (series b) were found to exhibit strong antinociceptive activity in the behavioural model. Among them, compound 1-diphenylacetyl-4-(4-methylphenyl)thiosemicarbazide 1b was found to be the most potentan algesic agent, whose activity is connected with the opioid system. For compounds from series a significant anti-serotonergic effect, especially for compound 1-diphenylacetyl-4- (4-methoxyphenyl)semicarbazide 2b was observed. The computational studies strongly support the obtained results

Antimicrobial and Physicochemical Characterizations of Thiosemicarbazide and <i>S</i>-Triazole Derivatives

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Biological evaluation and molecular modelling study of thiosemicarbazide derivatives as bacterial type IIA topoisomerases inhibitors

<div><p></p><p>In the present article, we describe the inhibitory potency of nine thiosemicarbazide derivatives against bacterial type IIA topoisomerases, their antibacterial profile and molecular modelling evaluation. We found that one of the tested compounds, compound <b>7</b>, significantly inhibits activity of <i>Staphylococcus aureus</i> DNA gyrase with an IC₅₀ below 15 μM. Besides, this compound displays antibacterial activity on reference <i>Staphylococuss</i> spp. and <i>Enterococcus faecalis</i> strains as well as clinical <i>S. aureus</i> isolates at non-cytotoxic concentrations in mammalian cells with MIC values ranging from 16 to 32 μg/mL thereby indicating, in some cases, equipotent or even more effective action than standard drugs such as vancomycin, ampicillin and nitrofurantoin. The computational studies showed that both molecular geometry and the electron density distribution have a great impact on antibacterial activity of thiosemicarbazide derivatives.</p></div

Search for human DNA topoisomerase II poisons in the group of 2,5-disubstituted-1,3,4-thiadiazoles

<div><p></p><p>A series of six 2,5-disubstituted 1,3,4-thiadiazole derivatives was synthesized and examined for cytotoxic activity in MCF-7 and MDA-MB-231 breast cancer cells. MTT assay confirmed that 2-(3-fluorophenylamino)-5-(3-hydroxyphenyl)-1,3,4-thiadiazole (<b>2</b>), 2-(4-bromophenylamino)-5-(2,4-dichlorophenyl)-1,3,4-thiadiazole (<b>3</b>), 2-(4-fluorophenylamino)-5-(2,4-dichlorophenyl)-1,3,4-thiadiazole (<b>4</b>), had ability to inhibit MCF-7 and MDA-MB-231 cells proliferation. The IC₅₀ values for the mentioned compounds ranged between 120 and 160 μM (with respect to MCF-7 cells) and from 70 to 170 μM (with respect to MDA-MB-231 cells). It turned out, moreover, that compound <b>2</b> is a human topoisomerase II (topoII) catalytic inhibitor whereas the two other compounds (i.e. <b>3</b> and <b>4</b>) are capable of stabilizing DNA-topoII cleavage complex and thus are topoII poisons.</p></div