950-07-2Relevant academic research and scientific papers
Ultrapotent Inhibitor of Clostridioides difficile Growth, Which Suppresses Recurrence in Vivo
Naclerio, George A.,Abutaleb, Nader S.,Li, Daoyi,Seleem, Mohamed N.,Sintim, Herman O.
, p. 11934 - 11944 (2020/11/26)
Clostridioides difficile is the leading cause of healthcare-associated infection in the U.S. and considered an urgent threat by the Centers for Disease Control and Prevention (CDC). Only two antibiotics, vancomycin and fidaxomicin, are FDA-approved for the treatment of C. difficile infection (CDI), but these therapies still suffer from high treatment failure and recurrence. Therefore, new chemical entities to treat CDI are needed. Trifluoromethylthio-containing N-(1,3,4-oxadiazol-2-yl)benzamides displayed very potent activities [sub-μg/mL minimum inhibitory concentration (MIC) values] against Gram-positive bacteria. Here, we report remarkable antibacterial activity enhancement via halogen substitutions, which afforded new anti-C. difficile agents with ultrapotent activities [MICs as low as 0.003 μg/mL (0.007 μM)] that surpassed the activity of vancomycin against C. difficile clinical isolates. The most promising compound in the series, HSGN-218, is nontoxic to mammalian colon cells and is gut-restrictive. In addition, HSGN-218 protected mice from CDI recurrence. Not only does this work provide a potential clinical lead for the development of C. difficile therapeutics but also highlights dramatic drug potency enhancement via halogen substitution.
Structural modification of cuminaldehyde thiosemicarbazone increases inhibition specificity toward aflatoxin biosynthesis and sclerotia development in Aspergillus flavus
Degola, Francesca,Bisceglie, Franco,Pioli, Marianna,Palmano, Sabrina,Elviri, Lisa,Pelosi, Giorgio,Lodi, Tiziana,Restivo, Francesco Maria
supporting information, p. 6683 - 6696 (2017/08/23)
Aspergillus flavus is an opportunistic mold that represents a serious threat for human and animal health due to its ability to synthesize and release, on food and feed commodities, different toxic secondary metabolites. Among them, aflatoxin B1 is one of the most dangerous since it is provided with a strong cancerogenic and mutagenic activity. Controlling fungal contamination on the different crops that may host A. flavus is considered a priority by sanitary authorities of an increasing number of countries due also to the fact that, owing to global temperature increase, the geographic areas that are expected to be prone to experience sudden A. flavus outbreaks are widening. Among the different pre- and post-harvest strategies that may be put forward in order to prevent fungal and/or mycotoxin contamination, fungicides are still considered a prominent weapon. We have here analyzed different structural modifications of a natural-derived compound (cuminaldehyde thiosemicarbazone) for their fungistatic and anti-aflatoxigenic activity. In particular, we have focused our attention on one of the compound that presented a prominent anti-aflatoxin specificity, and performed a set of physiological and molecular analyses, taking also advantage of yeast (Saccharomyces cerevisiae) cell as an experimental model.
Synthesis and antitubercular activity of 2-(1H-pyrrol-1-Yl)-5- substituted-1,3,4-oxadiazoles
Joshi, Shrinivas D.,Dixit, Sheshagiri R.,More, Uttam A.,Kulkarni, Venkatrao H.
, p. 137 - 140 (2019/01/21)
A series of 2-(1H-pyrrol-1-yl)-5-substituted-1,3,4-oxadiazole derivatives were prepared and evaluated for their antitubercular activity. These derivatives were synthesized by the reaction of 5-substituted-1,3,4-oxadiazol-2-amines (4a-j) with 2,5- dimethoxytetrahydrofuran in dried acetic acid. Structures of the newly synthesized compounds were confirmed on the basis of physico-chemical and spectral data. All the synthesized compounds were screened for their antitubercular activity using microplate almar blue assay (MABA) method. Compounds have shown moderate to good antitubercular activity against M. tuberculosis H37Rv microorganism.
Synthesis and in vitro antitumor activity of 1,3,4-oxadiazole derivatives based on benzisoselenazolone
Luo, Zhen-Hua,He, Shuang-Yan,Chen, Bao-Quan,Shi, Yan-Ping,Liu, Yu-Ming,Li, Cai-Wen,Wang, Qiu-Sheng
experimental part, p. 887 - 891 (2012/08/14)
A series of novel 1,3,4-oxadiazole derivatives based on benzisoselenazolone has been prepared and tested for antiproliferative activity in vitro against the cells of human cancer cell lines: SSMC-7721 (human liver cancer cell), MCF-7 (human breast cancer cell) and A549 (human lung cancer cell). All the compounds obtained exhibited antiproliferative activity and showed selective cytotoxicity against different cancer cells. Compounds 7d and 7i showed significant antiproliferative activities against MCF-7 cells, with IC50 values of 1.07 and 1.76/μM respectively. Compound 7d were found to be the most potent compound against SSMC-7721 cells, with IC50 values 4.46/μM.
