CORVALLIS, Ore. – A natural antibiotic long known for its power to fight bacteria, viruses and tumors has recently shown strength against malaria, but its extreme toxicity has impeded its use in medicine.
However, a bioengineering breakthrough has opened a new avenue in the global battle against malaria
Scientists at Oregon State University have engineered several new versions of the antibiotic pactamycin that are up to 30 times less toxic than the parent compound. The new compounds, whose genetic structures were modified in the lab, retain their potency against malaria-causing parasites yet pose fewer risks to patients.
“The results could lead to a new direction in the discovery and development of drugs against malaria and other life-threatening infections caused by protozoa,” said OSU researcher Taifo Mahmud, an author of the study reported in the journal Chemistry & Biology.
The natural form of pactamycin occurs in soil bacteria. It attacks not only protozoa such as the mosquito-borne P. falciparum, which causes malaria, but also bacteria, viruses and tumors. Unfortunately, it attacks healthy cells in mammals, as well. In an effort to capture pactamycin’s benefits while eliminating or minimizing its detriments, OSU researchers modified the genetic structure of the microbe that produces the antibiotic by inactivating or “knocking out” certain genes. They tested the new versions – called “analogues” – on human colorectal cancer cells.
“The results revealed that the new analogues are significantly less toxic than pactamycin,” said Mahmud, a medicinal chemist in the OSU College of Pharmacy.
Mahmud said the OSU study is a promising development in the struggle against malaria, which annually infects 250 million people and kills nearly 1 million worldwide, according to the World Health Organization.
“Although pactamycin was first reported in the 1960s and its various biological activities have been extensively investigated, further development of this compound was hampered by its wide-ranging cytotoxicity,” Mahmud said.
“The study resulted in a number of pactamycin analogues that showed potent antimalarial activity but, in contrast to pactamycin, have reduced cytotoxicity against mammalian cells.”