Inhibition of enterovirus 71 (EV-71) infections by a novel antiviral peptide derived from EV-71 capsid protein VP1.

Enterovirus 71 (EV-71) is the main causative agent of hand, foot and mouth disease (HFMD). In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers) overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD) cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC(50) values ranging from 6-9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71.

A new carbazole alkaloid from the leaves of Malayan Murraya koenigii.

New carbazole alkaloid, 7-hydroxymurrayazolinine (1), was isolated from the ethanol extract of the leaves of Malayan Murraya koenigii, together with five known carbazole alkaloids, mahanimbine (2), bicyclomahanimbine (3), girinimbine (4), koenimbine (5), and murrayamine-D (6). Their structures were elucidated on the basis of spectroscopic analysis.

Four tetracyclic oxindole alkaloids and a taberpsychine derivative from a Malayan Tabernaemontana.

Four tetracyclic oxindole alkaloids, 7(R)- and 7(S)-geissoschizol oxindole (1 and 2), 7(R),16(R)- and 7(S),16(R)-19(E)-isositsirikine oxindole (3 and 4), in addition to a taberpsychine derivative, N(4)-demethyltaberpsychine (5), were isolated from the Malayan Tabernaemontana corymbosa and the structures were established using NMR and MS analysis.

A new amide alkaloid from the leaves of Piper sarmentosum.

A new amide alkaloid, N-(3',4',5'-trimethoxy-cis-cinnamoyl)pyrrolidine (1), named sarmentomicine was isolated from the ethanol extract of the leaves of Malayan Piper sarmentosum, together with two known phenylpropanoids. Their structures were elucidated on the basis of spectroscopic analysis.

Leuconoxine, kopsinitarine, kopsijasmine, and kopsinone derivatives from Kopsia.

Four new indole alkaloids were obtained from two Kopsia species, 6-oxoleuconoxine (1) from the leaf extract of K. griffithii and kopsinitarine E (2), kopsijasminine (3), and kopsonoline (4) from the stem-bark extract of K. teoi. The structures of these alkaloids were determined using NMR and MS analysis. Kopsijasminine (3) showed moderate activity in reversing multidrug resistance in vincristine-resistant KB cells.

Cytotoxic effects and reversal of multidrug resistance by ibogan and related indole alkaloids.

A series of indole alkaloids of the ibogan-type was assessed for their cytotoxic effects as well as their potential in reversing MDR in vincristine-resistant KB cells. Of a total of 25 compounds tested, 3(S)-cyanocoronaridine, 3(S)-cyanoisovoacangine, 3(S)-cyanovoacangine, and 10,11-demethoxychippiine were found to show appreciable cytotoxicity toward KB cells, while coronaridine, heyneanine, 19-epi-heyneanine, dippinine B, and dippinine C, were found to reverse MDR in vincristine-resistant KB cells.

Conodurine, conoduramine, and ervahanine derivatives from Tabernaemontana corymbosa.

Four bisindole alkaloids, viz., 19'(S)-hydroxyconodurine, conodurinine, 19'(S)-hydroxyconoduramine, and 19'(S)-hydroxyervahanine A, in addition to conodurine and ervahanine A, were obtained from the leaf and stem-bark extracts of Tabernaemontana corymbosa. The structures of the new alkaloids were determined using NMR and MS analysis.

New bisindole alkaloids from Tabernaemontana corymbosa.

Ten new bisindole alkaloids of the vobasinyl-ibogan type, viz., conodiparines A-F (1-6), conodutarines A and B (7, 8), and cononitarines A and B (9, 10), were obtained from the leaf extract of the Malayan species Tabernaemontana corymbosa. The structures were determined using NMR and MS analysis.

Five new iboga alkaloids from Tabernaemontana corymbosa.

Five new indole alkaloids of the ibogan type (1-5), in addition to 12 other known iboga alkaloids, were obtained from the leaf and stem-bark extract of the Malayan species Tabernaemontana corymbosa, viz., 19(S)-hydroxyibogamine (1), 19-epi-isovoacristine (2), isovoacryptine (3), 3R/S-ethoxyheyneanine (4), and 3R/S-ethoxy-19-epi-heyneanine (5). The structures were determined using NMR and MS analysis and comparison with known related compounds.