692764-08-2Relevant articles and documents
New quinolone-based thiosemicarbazones showing activity against plasmodium falciparum and mycobacterium tuberculosis
Beteck, Richard M.,Seldon, Ronnett,Jordaan, Audrey,Warner, Digby F.,Hoppe, Heinrich C.,Laming, Dustin,Khanye, Setshaba D.
, (2019)
Co-infection of malaria and tuberculosis, although not thoroughly investigated, has been noted. With the increasing prevalence of tuberculosis in the African region, wherein malaria is endemic, it is intuitive to suggest that the probability of co-infection with these diseases is likely to increase. To avoid the issue of drug-drug interactions when managing co-infections, it is imperative to investigate new molecules with dual activities against the causal agents of these diseases. To this effect, a small library of quinolone-thiosemicarbazones was synthesised and evaluated in vitro against Plasmodium falciparum and Mycobacterium tuberculosis, the causal agents of malaria and tuberculosis, respectively. The compounds were also evaluated against HeLa cells for overt cytotoxicity. Most compounds in this series exhibited activities against both organisms, with compound 10, emerging as the hit; with an MIC90 of 2 μM against H37Rv strain of M. tuberculosis and an IC50 of 1 μM against the 3D7 strain of P. falciparum. This study highlights quinolone-thiosemicarabazones as a class of compounds that can be exploited further in search of novel, safe agents with potent activities against both the causal agents of malaria and tuberculosis.
Quinolone-isoniazid hybrids: Synthesis and preliminary: In vitro cytotoxicity and anti-tuberculosis evaluation
Beteck, Richard M.,Seldon, Ronnett,Jordaan, Audrey,Warner, Digby F.,Hoppe, Heinrich C.,Laming, Dustin,Legoabe, Lesetja J.,Khanye, Setshaba D.
, p. 326 - 331 (2019)
Herein, we propose novel quinolones incorporating an INH moiety as potential drug templates against TB. The quinolone-based compounds bearing an INH moiety attached via a hydrazide-hydrazone bond were synthesised and evaluated against Mycobacterium tuberculosis H37Rv (MTB). The compounds were also evaluated for cytotoxicity against HeLa cell lines. These compounds showed significant activity (MIC90) against MTB in the range of 0.2-8 μM without any cytotoxic effects. Compounds 10 (MIC90; 0.9 μM), 11 (MIC90; 0.2 μM), 12 (MIC90; 0.8 μM) and compound 15 (MIC90; 0.8 μM), the most active compounds in this series, demonstrate activities on par with INH and superior to those reported for the fluoroquinolones. The SAR analysis suggests that the nature of substituents at positions -1 and -3 of the quinolone nucleus influences anti-MTB activity. Aqueous solubility evaluation and in vitro metabolic stability of compound 12 highlights favourable drug-like properties for this compound class.
Synthesis and in vitro antitrypanosomal evaluation of novel 6-heteroarylidene-substituted quinolone derivatives
Angula, Klaudia T.,Beteck, Richard M.,Hoppe, Heinrich C.,Legoabe, Lesetja J.,Swart, Tarryn
, (2021/10/16)
Human African trypanosomiasis is a vector-borne tropical disease of African origin. Presently, due to human migration and climate change, the disease might present global health and economic burdens as current chemotherapy of trypanosomiasis remains a challenge due to limited existing drugs, which are of poor efficacy, cause severe adverse events and are very costly. Recently, Beteck and co-workers identified a small library of 1,3,6-substituted non-fluoroquinolones that showed moderate to weak trypanocidal activity without cytotoxic effects. The current study further explored SARs of the quinolone scaffold in search for more potent trypanocidal agents. Fifteen novel quinolone derivatives bearing a heteroarylidene moiety at positon-6 and varied chemical entities at positions ?1 and ?3 of the quinolone scaffold were synthesized and evaluated in vitro for antitrypanosomal activity. The compounds exhibit exceptionally good antitrypanosomal activity with IC50 values in the low-micromolar to sub-micromolar range (0.08–15.26 μM), with compound 6d being the most active having an IC50 value of 80 nM against T.b. brucei. Compounds in this study generally have molecular weight less than 600Da, ClogP value of 2–4 and a BBB score of 1–5, hence they could be potentially effective against both stages of trypanosomiasis.
Synthesis, in vitro cytotoxicity and trypanocidal evaluation of novel 1,3,6-substituted non-fluoroquinolones
Beteck, Richard M.,Isaacs, Michelle,Hoppe, Heinrich C.,Khanye, Setshaba D.
, p. 188 - 195 (2019/01/04)
Sleeping sickness (trypanosomiasis) is a neglected tropical disease that affects mostly the poorest communities in sub-Saharan Africa. Toxic side effects associated with the use of current anti-trypanosomal drugs, which in some cases kill faster than the
Discovery of plasmodium vivax N -myristoyltransferase inhibitors: Screening, synthesis, and structural characterization of their binding mode
Goncalves, Victor,Brannigan, James A.,Whalley, David,Ansell, Keith H.,Saxty, Barbara,Holder, Anthony A.,Wilkinson, Anthony J.,Tate, Edward W.,Leatherbarrow, Robin J.
supporting information; experimental part, p. 3578 - 3582 (2012/06/01)
N-Myristoyltransferase (NMT) is a prospective drug target against parasitic protozoa. Herein we report the successful discovery of a series of Plasmodium vivax NMT inhibitors by high-throughput screening. A high-resolution crystal structure of the hit com
QIUNOLIN-4-ONES AS INHIBITORS OF RETROVIRAL INTEGRASE FOR THE TREATMENT OF HIV, AIDS AND AIDS RELATED COMPLEX (ARC)
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Page/Page column 31-32, (2008/06/13)
Novel quinoline inhibitors of retroviral integrase, particularly HIV-1 integrase. The quinoline inhibitors are oxoquinolines of the following formula (I) that can be used for preventing or treating AIDS or HIV infection in a subject. Wherein Z is selected
