Cytotoxic diterpenes from roots of Crossopetalum gaumeri, a Celastraceae species from Yucatan Peninsula.
Four new diterpenes, crossogumerins A-D (1-4) along with six known ones (5-10) were isolated from the root bark of Crossopetalum gaumeri, an endemic medicinal plant from the Yucatan Peninsula. Their structures were elucidated on the basis of 1D and 2D NMR techniques, including HMQC, HMBC, and ROESY experiments. Compounds 1-5, 8-10 were evaluated for cytotoxicity against HeLa (carcinoma of the cervix) and Hep-2 (lung carcinoma) human tumor cells lines and against normal Vero cells (African green monkey kidney) in lag and log phase of growth. Podocarpane diterpenes, crossogumerin B (2) and nimbiol (10), exhibited the highest activity against HeLa cells (IC50 values of 3.1 and 8.1 μM, respectively), but also selectivity on Vero cells (SI 22.6 and 7.5, respectively). The preliminary SAR studies suggest that an epoxy moiety in ring B and a hydrogen bond-donor group strategically positioned in the diterpene core are important requirements for cytotoxicity and selectivity.
Facultad de Química, Universidad Autónoma de Yucatán, C 41 No. 421, Col. Industrial, C.P. 97150 Mérida, Yucatán, Mexico.
Gumersindo
G
Miron-Lopez
Instituto Universitario de Bio-Orgánica 'Antonio González', Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 2, 38206 Tenerife, Islas Canarias, Spain.
Isabel L
IL
Bazzocchi
Instituto Universitario de Bio-Orgánica 'Antonio González', Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 2, 38206 Tenerife, Islas Canarias, Spain.
Ignacio A
IA
Jimenez-Diaz
Departamento de Microbiología y Biología Celular, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 2, 38206 Tenerife, Islas Canarias, Spain.
Laila M
LM
Moujir
Facultad de Química, Universidad Autónoma de Yucatán, C 41 No. 421, Col. Industrial, C.P. 97150 Mérida, Yucatán, Mexico.
Ramiro
R
Quijano-Quiñones
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, 04510 México, D.F., Mexico.
Leovigildo
L
Quijano
Facultad de Química, Universidad Autónoma de Yucatán, C 41 No. 421, Col. Industrial, C.P. 97150 Mérida, Yucatán, Mexico. Electronic address: mrejon@uady.mx.
Gonzalo J
GJ
Mena-Rejon
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D029753:Celastraceae / Q000737:chemistry*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D004224:Diterpenes / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D018517:Plant Roots / Q000737:chemistry; D014709:Vero Cells
D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes
Celastraceae; Crossopetalum; Cytotoxicity; Podocarpane; Yucatán