ABSTRACT
Pregnane oligoglycoside, namely roylinine, and a pregnane derivative, namely marsgenin, have been isolated from chloroform-soluble extract of dried stem of Marsdenia roylei, and their structures were determined using ¹H-NMR, ¹³C-NMR, ¹H-¹H COSY, HSQC, TOCSY and FABMS spectral techniques as well as chemical degradation and derivatisation.
Subject(s)
Glycosides/isolation & purification , Marsdenia/chemistry , Pregnanes/isolation & purification , Chromatography, Thin Layer , Magnetic Resonance Spectroscopy , Spectrometry, Mass, Fast Atom BombardmentABSTRACT
A series of [4-(aryloxy)phenyl]cyclopropyl methanones were synthesized by reaction of different benzyl alcohols with 4-chloro-4'-fluorobutyrophenone in DMF in the presence of NaH/TBAB. The methanones were further reduced to respective methanols. The antitubercular activity of these compounds was evaluated in vitro against Mycobacterium tuberculosis H37Rv. Compounds 19, 21, 35, 36 and 37 have shown minimum inhibitory concentration (MIC) of 3.12 µg/mL, while compounds 14, 25 and 18 have shown MIC of 1.56 µg/mL and 0.78 µg/mL respectively. One of the compounds, cyclopropyl-4-[4-(2-piperidin-1-yl-ethoxy)benzyloxy]phenyl}methanol (36) showed 98% killing of intracellular bacilli in mouse bone marrow derived macrophages and was active against MDR, XDR and rifampicin clinical isolates resistant strains with MIC 12.5 µg/mL. Compound 36 was orally active in vivo in mice against M. tuberculosis H37Rv with an increase in MST by 6 days with 1 log reduction in the bacillary density in lungs as compared to control on 30th day after infection.
Subject(s)
Antitubercular Agents/pharmacology , Cyclopropanes/pharmacology , Methanol/pharmacology , Mycobacterium tuberculosis/drug effects , Animals , Antitubercular Agents/chemical synthesis , Antitubercular Agents/chemistry , Chlorocebus aethiops , Cyclopropanes/chemical synthesis , Cyclopropanes/chemistry , Female , Macrophages/drug effects , Methanol/analogs & derivatives , Methanol/chemical synthesis , Mice , Microbial Sensitivity Tests , Molecular Structure , Stereoisomerism , Structure-Activity Relationship , Vero CellsABSTRACT
The structure of pregnane oligoglycosides, namely rocinine (1) and marsdinine (11), which have been isolated from the chloroform soluble extract of the dried stem of Marsdenia roylei, were elucidated using MS, (1)H NMR, (13)C NMR, (1)H-(1)H COSY, HSQC and TOCSY experiments as well as chemical degradation and derivatisation.
