Search for highly-prized drugs in ‘lowly’ Vinca continues

UP Los Baños is currently employing biotechnology to produce clinically-important compounds from an erstwhile common garden plant – the Vinca. According to Dr. Eufrocinio Marfori of BIOTECH based at UP Los Baños, his team is looking for more natural products which can be derived from the Vinca.

VINCA AS A SOURCE OF DRUGS

Scientifically named Catharanthus roseus, Vinca is endemic to Madagascar. But now, this shrub can be found in almost any tropical area in the world. This shrub has oval to oblong leaves, white to dark pink flowers, and grows up to 1 meter tall. Possessing about 70 already identified chemical compounds; it has been exploited commercially as source of natural products such as alkaloids.

Alkaloids are chemical compounds which are naturally found in bacteria, fungi, plants, and animals. Using chemistry methods, alkaloids can be purified from crude extracts to produce pharmaceutical and recreational drugs.

At least two of the alkaloids in Vinca (vinblastine and vincristine) have been isolated and developed into prescription anti-cancer drugs in the 1950s and 1960s.

FIRST FORAY INTO DRUG DISCOVERY

In the early 1990’s Dr. William G. Padolina, then head of BIOTECH, started culturing and evaluating calluses from flowers of a mutant Vinca plant found in Zamboanga. Their group subsequently established a unique culture line of Vinca callus which was designated as BCr-1.

Plant calluses are undifferentiated cells which can be grown and maintained in a growing media. These materials have many uses, for example, mass propagation of identical copies of the plant and DNA insertion experiments.

High performance liquid chromatography analysis done in 1994 by Padolina’s group, which included then a young Marfori, showed that the vincristine alkaloid extract from their C. roseus calli was consistent with that of the authentic one.

ABOUT A DECADE LATER

By the late 1990s, as part of his doctoral dissertation studies, Dr. Marfori brought with him to Japan the BCr-1 Vinca callus for further experimentation. He and his advisers from Osaka University came up with an idea to see what compound can be produced if the BCr-1 callus is grown in a Murashige and Skoog agar medium and infected with Trichoderma harzianum – a fungus.

This type of growing method, called dual culture, is a known way to produce interactions between plant and fungus in the laboratory. When fungi infect calli, scenarios can evolve: new metabolites may be produced by the callus as a response to infection, or they may be produced by the fungus as it draws its nutrition from the callus.

In 2002, Dr. Marfori’s research created a novel antibiotic called trichosetin. In microbial assays, trichosetin showed a very strong antimicrobial activity against Methicilin-resistant Staphylococcus aureus (MRSA) and Bacillus subtilis

HUMAN AND POULTRY CURE IN THE PIPELINE

After returning to UPLB, Dr. Marfori conducted experiments to determine the efficacy and safety of trichosetin as a therapeutic agent for poultry. His results in 2007 showed that trichosetin inhibited a strain of Staphylococcus sp. which was already resistant to various drugs. It also exhibited moderate activity against Pasteurella multocida. More experiments afterwards showed that it was non-toxic to chicken and does not cause cells to mutate.

Dr. Marfori has recently reported that his group has conducted mutagenicity tests to assess the safety of use of trichosetin. According to the report, micronucleus tests and rec assays revealed that trichosetin is not mutagenic.

PEERING INTO THE ALKALOID UNIVERSE

With funding from the Department of Science and Technology, Dr. Marfori is now looking for other potential and prized compounds from the BCr-1 callus.

Only this year, using commonly used alkaloid extraction methods, he identified that the callus also produces ajmalicine – a compound for non-steroidal anti-inflammatory drugs and drugs for memory enhancement and chemotherapy.

Dr. Marfori is optimistic that with modern biotechnology and the Philippines vast natural resources, more researchers will pursue the goal of discovering and creating affordable drugs for Filipinos.

Published: 03 Apr 2009

Contact details:

c/o the Chancellor
University of the Philippines Los Baños
Abelardo Samonte Hall
UPLB, College, Laguna 4031

63495362567
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