A Bis-benzopyrroloisoquinoline Alkaloid Incorporating a Cyclobutane Core and a Chlorophenanthroindolizidine Alkaloid with Cytotoxic Activity from Ficus fistulosa var. tengerensis

Abstract

Tengerensine (1), isolated as a racemate and constituted from a pair of bis-benzopyrroloisoquinoline enantiomers, and tengechlorenine (2), purified as a scalemic mixture and constituted from a pair of chlorinated phenanthroindolizidine enantiomers, were isolated from the leaves of Ficus fistulosa var. tengerensis, along with three other known alkaloids. The structures of 1 and 2 were determined by spectroscopic data interpretation and X-ray diffraction analysis. The enantiomers of 1 were separated by chiral-phase HPLC, and the absolute configurations of (+)-1 and (-)-1 were established via experimental and calculated ECD data. Compound 1 is notable in being a rare unsymmetrical cyclobutane adduct and is the first example of a dimeric benzopyrroloisoquinoline alkaloid, while compound 2 represents the first naturally occurring halogenated phenanthroindolizidine alkaloid. Compound (+)-1 displayed a selective in vitro cytotoxic effect against MDA-MB-468 cells (IC 7.4 μM), while compound 2 showed pronounced in vitro cytotoxic activity against all three breast cancer cell lines tested (MDA-MB-468, MDA-MB-231, and MCF7; IC values of 0.038-0.91 μM).

Phosphoinositide‐dependent Kinase‐1 (PDPK1) regulates serum/glucocorticoid‐regulated Kinase 3 (SGK3) for prostate cancer cell survival

“…The plates were terminated by MTT cell proliferation assay at 72 hours after treatment. 23,24 Calcusyn 2.1 software (Biosoft, Cambridge, UK) was used to generate combination index (CI) based on Chou-Talalay method, 19,25 in which CI < 1, = 1 and >1 indicates synergism, additive and antagonism effect, respectively (Table S3). The dose-response surface curves with levels of HSA synergy were plotted by Combenefit software (Cancer Research UK Cambridge Institute).…”

Unraveling Plant Natural Chemical Diversity for Drug Discovery Purposes

“…Table 3 where the entries are in bold characters. (A) chlorinated phenanthroindolizidine (Al-Khdhairawi et al, 2017); (B) 3,4-seco-lupane-type triterpenoid ; (C) asteriscunolide C (Boumaraf et al, 2017); (D) (+)-strebloside ; (E) Glycybridin D ; (F) (-)-neocaryachine ; (G) plectranthroyleanone A (Nzogong et al, 2018); (H) uncarilin A (Geng et al, 2017); (I) 27-hydroxyalphitolic acid derivative (Novakovic et al, 2017) The following chemical names were given when the structures were fairly simple. For other more complex skelettons (AM, AP, AQ, AR, AU and AV), common names were given that correspond to the global structure of the core molecule.…”

Biologically active isoquinoline alkaloids covering 2014–2018

“…In this review, we list in Table 2 we found that most compounds exhibited moderate cytotoxicity with IC 50 values ranging from 10 to 50 μM. 22,25,27,33,38,40,45,46,53,68,80,[83][84][85][86][87][88]90,93,98,101,105,159 Three Amaryllidaceae alkaloids, lycorine (321), haemanthamine (326), and haemanthidine 327 Table 2. Higher antiproliferative effects also were reported.…”