A cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) technique has been developed for enantioseparation of vinpocetine using an inexpensive 2-hydroxypropyl-β-CD (HP-β-CD) as the chiral selector (CS). The best chiral separation was achieved using 40 mM HP-β-CD as the CS in 50 mM phosphate buffer (pH 7.0) consisting of 40 mM sodium dodecyl sulfate (SDS) at a separation temperature and separation voltage of 25°C and 25 kV, respectively. To the author's best knowledge, this is the first CD-MEKC study able to successfully separate the four stereoisomer of vinpocetine in separation time of 9.5 min and resolution of 1.04-3.87.
Reexamination of the absolute configuration of recently isolated eburnane alkaloids from Malaysian Kopsia and Leuconotis species by X-ray diffraction analysis and ECD/TDDFT has revealed the existence of biosynthetic enantiodivergence. Three different scenarios are discerned with respect to the composition of the enantiomeric eburnane alkaloids in these plants: first, where the new eburnane congeners possess the same C-20, C-21 absolute configurations as the common eburnane alkaloids (eburnamonine, eburnamine, isoeburnamine, eburnamenine) occurring in the same plant; second, where the new eburnane congeners possess opposite or enantiomeric C-20, C-21 absolute configurations compared to the common eburnane alkaloids found in the same plant; and, third, where the four common eburnane alkaloids were isolated as racemic or scalemic mixtures, while the new eburnane congeners were isolated as pure enantiomers with a common C-20, C-21 configuration (20α, 21α). Additionally, the same Kopsia species (K. pauciflora) found in two different geographical locations (Peninsular Malaysia and Malaysian Borneo) showed different patterns in the composition of the enantiomeric eburnane alkaloids. Revision of the absolute configurations of a number of new eburnane congeners (previously assigned based on the assumption of a common biogenetic origin to that of the known eburnane alkaloids co-occurring in the same plant) is required based on the present results.
Microtubule Targeting Agents (MTAs) including paclitaxel, colchicine and vinca alkaloids are widely used in the treatment of various cancers. As with most chemotherapeutic agents, adverse effects and drug resistance are commonly associated with the clinical use of these agents. Methyl 2-(5-fluoro-2-hydroxyphenyl)-1H- benzo[d]imidazole-5-carboxylate (MBIC), a benzimidazole derivative displays greater toxicity against various cancer compared to normal human cell lines. The present study, focused on the cytotoxic effects of MBIC against HeLa cervical cancer cells and possible actions on the microtubule assembly.
The biosynthesis of nanoparticles has been proposed as a cost-effective and environmental friendly alternative to chemical and physical methods. The present study was aimed to characterise Catharanthus roseus (C. roseus)-silver nanoparticles (AgNPs) using a standardised C. roseus aqueous extract. Methods: The standardisation was performed by using Liquid Chromatography/Time-of-Flight ion trap Mass Spectrometry. An optimised C. roseus-AgNPs have been previously synthesised. Further characterisation of C. roseus-AgNPs was evaluated by zeta potential analysis and fourier transform infrared spectroscopy (FTIR). Results: The chromatography analysis has revealed presence of thirteen possible indole alkaloids in C. roseus extract which were lochrovicine, lochnerine, vinleurosine, vindolinine, tabersonine, catharanthine, serpentine, catharosine, vincristine, catharine, ajmalicine, vinleurosine, and vindolicine. Zeta potential analysis exhibited the value at -16.6 mV. FTIR spectrum of C. roseus aqueous extract showed the absorption band at 3210.83 cm-1 (C-H stretch), 2934.11 (C-H bond), 1578.15 (N=O stretch), 1388.76 and 1314.89 (N=O bend), 1119.29 (C-O bond) and 729.94 (C-Cl bond). In comparison, FTIR spectrum of C. roseus-AgNP s showed the absorption band at 2925.01 and 2924.97 (C-H bond), 1622.93 (C-C=C symmetric stretch), 1383.19 and 1384.13 (N-O bend), 1037.92/1038.76/1238.3/1117.2 (C-O bond), 3169.4 (O-H bond), 774.59 and 691.53 (C-Cl bond). Conclusion: The present findings have shown that the C. roseus aqueous extract contains alkaloids that may responsible as reducing and stabilising agents in the synthesis of AgNPs.
A rapid and simple reversed phase liquid chromatographic system has been developed for simultaneous analysis of terpenoid indole alkaloids (TIAs) and their precursors. This method allowed separation of 11 compounds consisting of eight TIAs (ajmalicine, serpentine, catharanthine, vindoline, vindolinine, vincristine, vinblastine, and anhydrovinblastine) and three related precursors i.e., tryptophan, tryptamine and loganin. The system has been applied for screening the TIAs and precursors in Catharanthus roseus plant extracts. In this study, different organs i.e., flowers, leaves, stems, and roots of C. roseus were investigated. The results indicate that TIAs and precursor accumulation varies qualitatively and quantitatively in different organs of C. roseus. The precursors showed much lower levels than TIAs in all organs. Leaves and flowers accumulate higher level of vindoline, catharanthine and anhydrovinblastine while roots have higher level of ajmalicine, vindolinine and serpentine. Moreover, the alkaloid profiles of leaves harvested at different ages and different growth stages were studied. The results show that the levels of monoindole alkaloids decreased while bisindole alkaloids increased with leaf aging and upon plant growth. The HPLC method has been successfully applied to detect TIAs and precursors in different types of C. roseus samples to facilitate further study of the TIA pathway and its regulation in C. roseus plants.
Flowers of Tabernaemontana divaricata (L.) R. Br., (Apocynaceae) are used in traditional medicine for analgesic property. The present study was performed to isolate the active principles and investigate the mechanisms involved in the anti-nociception caused by T. divaricata flower methanolic extract (TDFME). The extract in the doses of 125, 250 and 500 mg/kg, p.o was subjected to various assays in acetic acid induced abdominal writhing and formalin induced paw licking test models. Naloxone, L-Arginine, Glibenclamide and Glutamate were used as inducers while Morphine, L-NAME, Methylene blue and Aspirin served as standard drugs. The phytochemical analysis led to the isolation of three indole alkaloids namely Voacangine, Catharanthine and O-acetyl Vallesamine. The anti-nociception produced by TDFME was attenuated significantly (p< 0.001) by the intra-peritoneal pretreatment of naloxone, L-Arginine and glibenclamide. The nociception produced by glutamate was inhibited by TDFME. TDFME also enhanced the antinociceptive activity of L-NAME when given in combination. However TDFME co-administration did not produce significant results with methylene blue indicating lack of cGMP involvement. These results indicate that TDFME produces anti-nociception action mediated by opioid, nitric oxide, K+-ATP and glutamate mechanisms and the effect is largely related to the indole alkaloids.
Natural products with immunomodulatory activity are widely used in treatment of many diseases including autoimmune diseases, inflammatory disorders in addition to cancer. They gained a great interest in the last decades as therapeutic agents since they provide inexpensive and less toxic products than the synthetic chemotherapeutic agents. Immunomodulators are the agents that have the ability to boost or suppress the host defense response that can be used as a prophylaxis as well as in combination with other therapeutic modalities. The anticancer activity of these immunomodulators is due to their anti-inflammatory, antioxidant, and induction of apoptosis, anti-angiogenesis, and anti-metastasis effect. These natural immunomodulators such as genistein, curcumin, and resveratrol can be used as prophylaxis against the initiation of cancer besides the inhibition of tumor growth and proliferation. Whereas, immunostimulants can elicit and activate humoral and cell-mediated immune responses against the tumor that facilitate the recognition and destruction of the already existing tumor. This review represents the recent studies on various natural immunomodulators with antitumor effects. We have focused on the relationship between their anticancer activity and immunomodulatory mechanisms. The mechanisms of action of various immunomodulators such as polyphenolic compounds, flavonoids, organosulfur compounds, capsaicin, vinca alkaloids, bromelain, betulinic acid and zerumbone, the affected cancerous cell lines in addition to the targeted molecules and transcriptional pathways have been review and critically analyzed.