(+)/(−)-Phaeocaulin A-D, four pairs of new enantiomeric germacrane-type sesquiterpenes from Curcuma phaeocaulis as natural nitric oxide inhibitors

Abstract

Germacrane-type sesquiterpenes, with a flexible 10-membered ring unit as the structural and conformational features, play a central role in the biosynthesis and synthesis of other sesquiterpenes. In this report, two pairs of new sesquiterpene alkaloids, (+)/(−)-phaeocaulin A [(+)-1/(−)-1] and B [(+)-2/(−)-2], and two pairs of new sesquiterpenes, (+)/(−)-phaeocaulin C [(+)-3/(−)-3] and D [(+)-4/(−)-4], along with one related known analog (5), were isolated from the rhizomes of Curcuma phaeocaulis. The absolute configurations of (+)-1/(−)-1, (+)-2/(−)-2, (+)-3/(−)-3 and (+)-4/(−)-4 were unambiguously determined by analysis of single-crystal X-ray diffractions and quantum chemical electronic circular dichroism (ECD) method. It is noteworthy that (+)/(−)-phaeocaulin A [(+)-1/(−)-1] and B [(+)-2/(−)-2] are two pairs of rare N-containing germacrane-type sesquiterpenes. A possible biogenetic pathway for 1–5 was postulated. All of the isolated compounds were tested for their inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages.

Role of Calcium Sensing Receptor in Streptozotocin-Induced Diabetic Rats Exposed to Renal Ischemia Reperfusion Injury

“…NO is biosynthesized endogenously from L-arginine, oxygen, and NADPH by various NOS enzymes, playing a role in a variety of biological processes [36]. To evaluate the inflammatory reactions, the levels of IL-10 (anti-inflammatory factor) and IL-6 (pro-inflammatory factor) in the renal tissue were also measured.…”

Role of Nitric Oxide in Neurodegeneration: Function, Regulation, and Inhibition

“…experimented with some isolated phytoconstituents from Curcuma phaeocaulis concerning their inhibitory effect on NO production and found that several compounds had moderate inhibitory effects on NO synthesis with the range of IC50 values of 17.34 to 30.02 µM. However, the mechanisms of action of these compounds remained unexplored [ 149 ]. The NO inhibitory effects of phacadinanes A–D, which are four cadinane-type sesquiterpenes isolated from C. phaeocaulis, were examined in LPS-activated macrophages and it was found that two of these compounds possessed strong inhibitory activities with IC50 values of 3.88±0.58 and 2.25±0.71 μM [ 150 ].…”

Natural Enantiomers: Occurrence, Biogenesis and Biological Properties

“…Qiu and coworkers reported four pairs of megastigmane-type norsesquiterpenoid enantiomers 315a/315b−317a/317b and 325a/325b from Eucommia ulmoides in 2017, while the racemic mixtures of 315 and 325, along with pure enantiomers 316b and 317b, had been previously reported [163]. Compounds 318a/318b and 319a/319b are two pairs of enantiomeric germacrane type sesquiterpenes from Curcuma phaeocaulis reported in 2017 [128]. Chai and colleagues discovered 320a/320b−324a/324b with a humulane framework and 329a/329b incorporating a rare 2,2,5,9-tetramethylbicyclo[6.3.0]-undecane skeleton from Syringa pinnatifolia [164].…”

“…configs. by using modified Mother's method [83], and two pairs of germacrane-type sesquiterpenoid lactams 239 and 240 were obtained from Curcuma phaeocaulis by Qiu and colleagues [128]. Compounds 241a/241b and 242a/242b are flavonoid alkaloid enantiomers reported from Scutellaria moniliorrhiza in 2018 [129], while 243a/243b represent a pair of 9,10-dihydrophenanthrene alkaloid enantiomers from Bletilla striata [130].…”