Phytochemical, Synthetic and Biological Studies on Stemona and Stichoneuron Plants and Alkaloids: A Personal Perspective

This report is an overview of our research on phytochemical, synthetic and biological studies of the Stemona and Stichoneuron species of plants

Synthesis of stemofoline analogues as acetylcholinesterase inhibitors

Thirty-two new stemofoline analogues were prepared from didehydrostemofoline for studies as AChE inhibitors. C-3 Side-chain modified amino, carbamate, triazole and oxazole stemofoline derivatives were prepared. In general the amine derivatives were found to be stronger inhibitors of AChE than their alcohol analogues that we previously reported. Compounds 5 and 26, with small C-3 side-chain substituents, were two of the most active inhibitors. Preliminary molecular docking studies suggested that these compounds may inhibit AChE by binding horizontally along the passage of the active-site gorge and block access to acetylcholine. © 2012 Elsevier Ltd. All rights reserved

Inhibition of P-glycoprotein mediated multidrug resistance by stemofoline derivatives

Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATPbinding cassette (ABC) drug transporters including P-glycoprotein (P-gp) that actively efflux chemotherapeutic drugs from cancer cells. We examined the mutidrug resistance reversing property of stemofoline derivatives in drug-resistance human cervical carcinoma (KB-V1) and human leukemic (K562/Adr) cell lines that overexpress P-gp. Didehydrostemofoline and eleven of its derivatives were synthesized and the cytotoxicity and their effect on doxorubicin, vinblastine and paclitaxel sensitivity in drug resistant (KB-V1 and K562/ Adr) and drug sensitive (KB-3-1 and K562) cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were determined. We found that three out of the twelve stemofoline derivatives including OH-A1, NH-B6 and NH-D6 showed commitment efficiency to increase sensitivity to doxorubicin, vinblastine and paclitaxel in KB-V1 cells and increase sensitivity to doxorubicin, and paclitaxel in K562/Adr cells whereas the effects have not been seen in their parental sensitive cancer cell lines (KB-3-1 and K562). These results indicate that stemofoline derivatives reversed P-gp-mediated multidrug resistance in vitro, and thus could be developed as effective chemosensitizers to treat multidrug-resistant cancers. The molecular mechanism of modulation of P-gp would be further determined. © 2013 The Pharmaceutical Society of Japan

Influence of Salicylic Acid on Alkaloid Production by Root Cultures of Stemona curtisii Hook. F.

To enhance the production of oxyprotostemonine, stemocurtisine and stemocurtisinol (the important insecticidal alkaloids) by root cultures of Stemona curtisii Hook. F. (Thai vernacular, Non Tai Yak, Family Stemonaceae). The roots were cultured on semi-solid MS medium containing 1 mg/L NAA with different concentrations of salicylic acid for 16 weeks. The quantity of the individual alkaloids was determined by HPLC. The highest production of oxyprotostemonine (7.192 mg/g dw), stemocurtisine (0.039 mg/g dw) and stemocurtisinol (0.197 mg/g dw) occurred when the roots were stimulated by 500 mg/L salicylic acid

Structural revision of Stemoburkilline from an E-alkene to a Z-alkene

Semisynthesis studies starting from (11Z)-1′,2′- didehydrostemofoline (4) indicated that the known Stemona alkaloid stemoburkilline is the Z-isomer and not the E-isomer as initially reported. The semisynthesis involved conversion of (11Z)-1′,2′- didehydrostemofoline (4) to 11(S),12(S)-dihydrostemofoline (3) followed by a stereoselective base-catalyzed ring-opening reaction to give (Z)-stemoburkilline (8). The same product was obtained using a similar synthetic protocol starting from isostemofoline (6) via a based-catalyzed ring-opening reaction of 11(S),12(R)-dihydrostemofoline (1). A re-examination of the crude root extracts of Stemona burkillii Prain and further NOE studies established stemoburkilline as the Z-isomer (8). © 2009 American Chemical Society and American Society of Pharmacognosy

Phytochemical studies on stemona plants: Isolation of new tuberostemonine and stemofoline alkaloids

Two new tuberostemonine alkaloids, tuberostemonine L (3) and tuberostemonine M (4) and a new stemofoline alkaloid, (3'S)-hydroxystemofoline (5), along with two known alkaloids, (2'S)-hydroxystemofoline (1) and neotuberostemonine (2) have been isolated from a root extract of an unidentified Stemona species (Stemona sp.). The structure and relative configuration of these new alkaloids has been determined by spectral data interpretation, while the 3'S configuration of 5 was determined from NMR analysis of its (R)- and (S)-Mosher esters

Influence of Salicylic Acid on Alkaloid Production by Root Cultures of

Abstract: To enhance the production of oxyprotostemonine, stemocurtisine and stemocurtisinol (the important insecticidal alkaloids) by root cultures of Stemona curtisii Hook. F. (Thai vernacular, Non Tai Yak, Family Stemonaceae). The roots were cultured on semi-solid MS medium containing 1 mg/L NAA with different concentrations of salicylic acid for 16 weeks. The quantity of the individual alkaloids was determined by HPLC. The highest production of oxyprotostemonine (7.192 mg/g dw), stemocurtisine (0.039 mg/g dw) and stemocurtisinol (0.197 mg/g dw) occurred when the roots were stimulated by 500 mg/L salicylic acid