Matches in SemOpenAlex for { <https://semopenalex.org/work/W4293511063> ?p ?o ?g. }
- W4293511063 endingPage "984" @default.
- W4293511063 startingPage "984" @default.
- W4293511063 abstract "The continuous, worldwide spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) endanger the World Health Organization's (WHO) goal to end the global TB pandemic by the year 2035. During the past 50 years, very few new drugs have been approved by medical agencies to treat drug-resistant TB. Therefore, the development of novel antimycobacterial drug candidates to combat the threat of drug-resistant TB is urgent. In this work, we developed and optimized a total synthesis of the antimycobacterial natural flavonoid chlorflavonin by selective ruthenium(II)-catalyzed ortho-C(sp2)-H-hydroxylation of a substituted 3'-methoxyflavonoid skeleton. We extended our methodology to synthesize a small compound library of 14 structural analogs. The new analogs were tested for their antimycobacterial in vitro activity against Mycobacterium tuberculosis (Mtb) and their cytotoxicity against various human cell lines. The most promising new analog bromflavonin exhibited improved antimycobacterial in vitro activity against the virulent H37Rv strain of Mtb (Minimal Inhibitory Concentrations (MIC90) = 0.78 μm). In addition, we determined the chemical and metabolic stability as well as the pKa values of chlorflavonin and bromflavonin. Furthermore, we established a quantitative structure-activity relationship model using a thermodynamic integration approach. Our computations may be used for suggesting further structural changes to develop improved derivatives." @default.
- W4293511063 created "2022-08-30" @default.
- W4293511063 creator A5002848963 @default.
- W4293511063 creator A5004343189 @default.
- W4293511063 creator A5009835769 @default.
- W4293511063 creator A5015276222 @default.
- W4293511063 creator A5017078335 @default.
- W4293511063 creator A5017570068 @default.
- W4293511063 creator A5026996541 @default.
- W4293511063 creator A5032248952 @default.
- W4293511063 creator A5042635367 @default.
- W4293511063 creator A5053550707 @default.
- W4293511063 creator A5058839240 @default.
- W4293511063 creator A5061638239 @default.
- W4293511063 creator A5062986643 @default.
- W4293511063 creator A5063949219 @default.
- W4293511063 date "2022-08-10" @default.
- W4293511063 modified "2023-10-15" @default.
- W4293511063 title "Total Synthesis of the Antimycobacterial Natural Product Chlorflavonin and Analogs via a Late-Stage Ruthenium(II)-Catalyzed ortho-C(sp2)-H-Hydroxylation" @default.
- W4293511063 cites W1583489507 @default.
- W4293511063 cites W1602353974 @default.
- W4293511063 cites W1893960647 @default.
- W4293511063 cites W18986559 @default.
- W4293511063 cites W1964245683 @default.
- W4293511063 cites W1965680834 @default.
- W4293511063 cites W1966793020 @default.
- W4293511063 cites W1969873373 @default.
- W4293511063 cites W1973066355 @default.
- W4293511063 cites W1978987032 @default.
- W4293511063 cites W1996998349 @default.
- W4293511063 cites W2018430005 @default.
- W4293511063 cites W2024983608 @default.
- W4293511063 cites W2027065525 @default.
- W4293511063 cites W2038640032 @default.
- W4293511063 cites W2040938839 @default.
- W4293511063 cites W2048511854 @default.
- W4293511063 cites W2071183229 @default.
- W4293511063 cites W2072292761 @default.
- W4293511063 cites W2076552452 @default.
- W4293511063 cites W2077223881 @default.
- W4293511063 cites W2079175365 @default.
- W4293511063 cites W2100300015 @default.
- W4293511063 cites W2101383079 @default.
- W4293511063 cites W2103428939 @default.
- W4293511063 cites W2106084243 @default.
- W4293511063 cites W2118233996 @default.
- W4293511063 cites W2123203611 @default.
- W4293511063 cites W2131288855 @default.
- W4293511063 cites W2131643298 @default.
- W4293511063 cites W2134989724 @default.
- W4293511063 cites W2144465276 @default.
- W4293511063 cites W2146049267 @default.
- W4293511063 cites W2147241419 @default.
- W4293511063 cites W2157761965 @default.
- W4293511063 cites W2231113509 @default.
- W4293511063 cites W2339051409 @default.
- W4293511063 cites W2340910083 @default.
- W4293511063 cites W2461688213 @default.
- W4293511063 cites W248023317 @default.
- W4293511063 cites W2571178759 @default.
- W4293511063 cites W2744406893 @default.
- W4293511063 cites W2767223743 @default.
- W4293511063 cites W2785609333 @default.
- W4293511063 cites W2802798634 @default.
- W4293511063 cites W2803082205 @default.
- W4293511063 cites W2883408915 @default.
- W4293511063 cites W2894642145 @default.
- W4293511063 cites W2904807898 @default.
- W4293511063 cites W2946457584 @default.
- W4293511063 cites W2949543083 @default.
- W4293511063 cites W2950147977 @default.
- W4293511063 cites W2979103481 @default.
- W4293511063 cites W2982897949 @default.
- W4293511063 cites W3087701635 @default.
- W4293511063 cites W3095971278 @default.
- W4293511063 cites W4200241760 @default.
- W4293511063 cites W4211029352 @default.
- W4293511063 cites W4235629118 @default.
- W4293511063 doi "https://doi.org/10.3390/ph15080984" @default.
- W4293511063 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36015133" @default.
- W4293511063 hasPublicationYear "2022" @default.
- W4293511063 type Work @default.
- W4293511063 citedByCount "1" @default.
- W4293511063 countsByYear W42935110632023 @default.
- W4293511063 crossrefType "journal-article" @default.
- W4293511063 hasAuthorship W4293511063A5002848963 @default.
- W4293511063 hasAuthorship W4293511063A5004343189 @default.
- W4293511063 hasAuthorship W4293511063A5009835769 @default.
- W4293511063 hasAuthorship W4293511063A5015276222 @default.
- W4293511063 hasAuthorship W4293511063A5017078335 @default.
- W4293511063 hasAuthorship W4293511063A5017570068 @default.
- W4293511063 hasAuthorship W4293511063A5026996541 @default.
- W4293511063 hasAuthorship W4293511063A5032248952 @default.
- W4293511063 hasAuthorship W4293511063A5042635367 @default.
- W4293511063 hasAuthorship W4293511063A5053550707 @default.
- W4293511063 hasAuthorship W4293511063A5058839240 @default.
- W4293511063 hasAuthorship W4293511063A5061638239 @default.
- W4293511063 hasAuthorship W4293511063A5062986643 @default.