During recent years, small molecules containing five-member heterocyclic moieties have become the subject of considerable growing interest for designing new antitumor agents. One of them is 1,3,4-thiadiazole. This study is an attempt to collect the 1,3,4-thiadiazole and its derivatives, which can be considered as potential anticancer agents, reported in the literature in the last ten years.
We designed and synthesized the 1,3,4-thiadiazole derivatives differing in the structure of the substituents in C2 and C5 positions. The cytotoxic activity of the obtained compounds was then determined in biological studies using MCF-7 and MDA-MB-231 breast cancer cells and normal cell line (fibroblasts). The results showed that in both breast cancer cell lines, the strongest anti-proliferative activity was exerted by 2-(2-trifluorometylophenylamino)-5-(3-methoxyphenyl)-1,3,4-thiadiazole. The IC50 values of this compound against MCF-7 and MDA-MB-231 breast cancer cells were 49.6 µM and 53.4 µM, respectively. Importantly, all new compounds had weaker cytotoxic activity on normal cell line than on breast cancer cell lines. In silico studies demonstrated a possible multitarget mode of action for the synthesized compounds. The most likely mechanism of action for the new compounds is connected with the activities of Caspase 3 and Caspase 8 and activation of BAX proteins.
The emergence of drug-resistant bacterial strains continues to be one of the major challenges of medicine. For this reason, the importance of searching for novel structures of antibacterial drugs chemically different from the currently known antibiotics is still of great importance. In this study, we synthesized the thiosemicarbazide and 1,3,4-thiadiazole derivatives and tested them for antibacterial activity. In in vitro tests, we examined the activity of the synthesized substances against Gram-positive and Gram-negative bacteria strains. While all 1,3,4-thiadiazoles tested lacked significant activity, the antimicrobial response of the thiosemicarbazides was moderate and it was also dependent on the type and position of the substituent on the phenyl ring. The highest activity towards all Gram-positive bacteria strains was shown by all three linear compounds containing the trifluoromethylphenyl group in the structure. The MIC (minimum inhibitory concentration) values were in the range of 3.9–250 µg/mL. Additionally, we try to explain the mechanism of the antibacterial activity of the tested compounds using the molecular docking to DNA gyrase and topoisomerase IV, following previous reports on the molecular basis of the activity of thiosemicarbazides. Docking simulations allow the purposing dual mechanism of the antibacterial activity of the synthesized compounds through inhibition of topoisomerase IV DNA gyrase with the moderate prevalence of the topoisomerase pathway.
Based on the results of previous work, we designed and synthesized 1,3,4-thiadiazole derivatives. The cytotoxic activity of the obtained compounds was then determined in biological studies using MCF-7 and MDA-MB-231 breast cancer cells and a normal cell line (fibroblasts). The results showed that all compounds displayed weak anticancer activity towards two breast cancer lines: an estrogen-dependent cell line (MCF-7) and an estrogen-independent cell line (MDA-MB-231). The compound most active towards MCF-7 breast cancer cells was SCT-4, which decreased DNA biosynthesis to 70% ± 3 at 100 µM. The mechanism of the anticancer action of 1,3,4-thiadiazole was also investigated. We choose a set of the most investigated proteins, which are attractive anticancer targets. In silico studies demonstrated a possible multitarget mode of action for the synthesized compounds but the most likely mechanism of action for the new compounds is connected with the activity of caspase 8.
The series of novel Mannich bases were synthesized and evaluated for their in vitro antibacterial activity against Gram‐positive and Gram‐negative bacterial strains. The results showed that all compounds were less active than the drugs used as reference, but some of them had moderate potency against Staphylococcus epidermidis ATCC 12228 and Bacillus subtilis ATCC 6633. The presence of a phenyl ring in the position 4 of piperazine seems to be necessary for antibacterial activity in this class of compounds.
The treatment of infectious diseases is a challenging issue faced by the medical community. The emergence of drug-resistant strains of bacteria and fungi is a major concern. Researchers and medical professionals are working to develop new and innovative treatments for infectious diseases. Schiff bases are one a promising class of compounds. In this work, new derivatives were obtained of the 4-amino-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione reaction, with corresponding benzaldehydes with various substituents at position 4. The antibacterial and antifungal activities of all synthesized compounds were tested. Several new substances have shown moderate antifungal activity against Candida spp. The highest activity directed against C. albicans was shown by compound RO4, with a 4-methoxyphenyl moiety and an MIC value of 62.5 µg/mL. In order to check the toxicity of the synthesized compounds, their effect on cell lines was examined. Additionally, we tried to elucidate the mechanism of the antibacterial and antifungal activity of the tested compounds using molecular docking to topoisomerase IV, D-Alanyl-D-Alanine Ligase, and dihydrofolate reductase.
Targeting sonic hedgehog pathway in combination with proton radiation or gamma irradiation decreases viability of glioma cell lines .
W ostatnich latach związki o właściwościach antyoksydacyjnych występujące w roślinach – ze względu na ich zdolność neutralizacji wolnych rodników – cieszą się dużym zainteresowaniem naukowców. Zakłada się, że wolne rodniki mogą uczestniczyć w powstawaniu wielu chorób, zwłaszcza cywilizacyjnych, których liczba drastycznie rośnie. Mszaki stanowią wciąż słabo przebadaną grupę roślin, przez co są ciekawym obiektem badań fitochemicznych. Celem pracy było określenie potencjału antyoksydacyjnego ekstraktów z dwudziestu gatunków mchów. Badaniom poddano ekstrakty etanolowe z gametofitofitów dwudziestu gatunków mchów. W pracy wykorzystano następujące metody: metodę pomiaru zdolności zmiatania syntetycznego rodnika DPPH, metodę pomiaru zdolności chelatowania jonów żelaza (II). Na podstawie wyników uzyskanych z wykorzystaniem powyższych metod można stwierdzić, że ekstrakty ze wszystkich gatunków użytych w badaniach wykazują zdolność zmiatania wolnych rodników oraz zdolność do wiązania jonów żelaza (II). Najniższą aktywność antyoksydacyjną w próbach z wykorzystaniem metody zmiatania syntetycznego rodnika DPPH wykazały ekstrakty z gatunków: Polustriella commutata (IC50 = 264,52 mg/ml), Sphanum fimbriatum (IC50 = 154,66 mg/ml) oraz Pleurozium schreberi (IC50 = 126,81 mg/ml). Najwyższą zdolność chelatacji jonów żelaza wykazują ekstrakty: Hypnum cupres-siforme (IC50 = 0,32 mg/ml) oraz Rhytidiadelphus triquetrus (IC50 = 0,50 mg/ml). Przeprowadzone badania wykazały potencjał antyoksydacyjny 20 gatunków mchów. Najwyższy potencjał neutralizacji wolnego rodnika DPPH wykazały mchy z rodziny Polytrichopsida.
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