ABSTRACT
Seven new indole alkaloids of the Aspidosperma type, jerantinines A-G (1-7), were isolated from a leaf extract of the Malayan Tabernaemontana corymbosa. The structures were established using NMR and MS analysis. Five of the alkaloids isolated and two derivatives (1-5, 8, 9) displayed pronounced in vitro cytotoxicity against human KB cells (IC50 < 1 microg/mL).
Subject(s)
Indole Alkaloids/isolation & purification , Indole Alkaloids/pharmacology , Plants, Medicinal/chemistry , Tabernaemontana/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Drug Screening Assays, Antitumor , Humans , Indole Alkaloids/chemistry , KB Cells , Malaysia , Molecular Structure , Plant Leaves/chemistryABSTRACT
Ten new indole alkaloids of the aspidofractinine type, in addition to several recently reported indole alkaloids and 20 other known alkaloids, were obtained from the leaf and stem-bark extract of the Malayan Kopsia singapurensis, viz., kopsimalines A-E (1-5), kopsinicine (6), kopsofinone (7), and kopsiloscines H-J (8-10). The structures of these alkaloids were determined using NMR and MS analysis. Kopsimalines A (1), B (2), C (3), D (4), and E (5) and kopsiloscine J (10) were found to reverse multidrug-resistance in vincristine-resistant KB cells, with 1 showing the highest potency.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Apocynaceae/chemistry , Indole Alkaloids/isolation & purification , Indole Alkaloids/pharmacology , Plants, Medicinal/chemistry , Vincristine/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Drug Resistance, Neoplasm/drug effects , Drug Screening Assays, Antitumor , Humans , Indole Alkaloids/chemistry , KB Cells , Malaysia , Molecular Structure , Plant Bark/chemistry , Plant Leaves/chemistryABSTRACT
Eleven new indole alkaloids, in addition to the previously reported rhazinal (1), and 14 other known alkaloids, were obtained from the Malayan Kopsia singapurensis, viz., kopsiloscines A-F (2-7), 16-epikopsinine (8), kopsilongine- N-oxide (9), 16-epiakuammiline (10), aspidophylline A (11), and vincophylline (12). The structures of these alkaloids were determined using NMR and MS analyses. Rhazinal (1), rhazinilam (17), and rhazinicine (18) showed appreciable cytotoxicity toward drug-sensitive as well as vincristine-resistant KB cells, while kopsiloscines A (2), B (3), and D (5) and aspidophylline A (11) were found to reverse drug-resistance in drug-resistant KB cells.
Subject(s)
Alkaloids/isolation & purification , Alkaloids/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Plants, Medicinal/chemistry , Alkaloids/chemistry , Alkaloids/classification , Antineoplastic Agents, Phytogenic/chemistry , Drug Resistance, Multiple/drug effects , Drug Resistance, Neoplasm/drug effects , Drug Screening Assays, Antitumor , Humans , Indolizines/chemistry , Indolizines/isolation & purification , Indolizines/pharmacology , KB Cells , Lactams/chemistry , Lactams/isolation & purification , Lactams/pharmacology , Malaysia , Molecular StructureABSTRACT
Nine new indole alkaloids, rhazinoline (1), 19(S)-methoxytubotaiwine (2), 19(R)-methoxytubotaiwine (3), kopsamidine A (4), kopsamidine B (5), kopsinidine A (6), kopsinidine B (7), paucidactine C (8), and pericine N-oxide (9), in addition to several recently reported novel indoles and 34 other known ones, were obtained from the stem-bark extract of the Malayan Kopsia arborea. The structures were determined using NMR and MS analysis. Valparicine (12) showed pronounced cytotoxic effects against KB and Jurkat cells (IC(50) 13.0 and 0.91 microM, respectively).