Garden soil houses a number of bacteria and their natural by-products – including one that can help stop tumor growth. Lancacidins are molecules that can be isolated from Strepomyces rochei, a common bacterium in the soil. In addition to antimicrobial properties, a type of lankacidin, called lankacidin C, can inhibit tumor activity in various cancer cell lines, including leukemia, melanoma, ovarian and breast cancer. Lancacidin C offers a potential basis for designing cancer drugs, but its structure is complicated and difficult to manipulate, according to an international research team. The same group has recently identified where antitumor activity is located on the molecule and has now used this information to simplify lankacidin as a potential starting point for engineering treatments.
They published their results on January 1 in Bioorganic and medicinal chemistry.
“Lancacidins have potential antitumor agents, but their structural modification has some problem due to the presence of complex bicyclic ring in lankacidin antibiotics,” said paper author Kenji Arakawa, an associate professor at Hiroshima University’s Graduate School of Integrated Sciences for Life. “Structural modification of lankacidin C, as a parent compound, would be an excellent starting point for improving antitumor activity through computational prediction.”
The researchers tentatively assessed how different components of lankacidin group antibiotics could contribute to its antitumor activity using a computational model, and found that a structural ring of carbon atoms, called the delta-lactone ring, may not be crucial. According to Arakawa, the implication was striking, as the ability to structurally modify lankacidins has been limited by the presence of the delta-lactone ring.
“In this study, we synthesized lankacyclinone C, a new lankacidin C variant that lacks the delta-lactone ring,” Arakawa said. “By doing so, we solved a major problem with structural function of the lankacidin skeleton, the bicyclic structure of the delta-lactone ring, for antitumor activity.”
They used a protein called Orf23 to transform the bicyclic structure of the delta-lactone ring into a monocyclic version. A computational model predicted that the resulting lankacyclinone C, with a simplified ring, would still prove to be cytotoxic to cancer cells. Experimental results supported the prediction.
“Instead of bicyclic lankacidines, structurally simple and flexible monocyclic lankacidines may be better substrates for further structural redesign to improve antitumor activity,” Arakawa said.
According to Arakawa, the researchers plan to further investigate the rational design of molecular compounds with the goal of creating the ultimate antitumor agents.
Bicyclic protein mimetics inhibit the oncogenic β-catenin
Rukman Muslimin et al., Chemoenzymatic synthesis, computational study and antitumor activity of monocyclic lankacidin derivatives, Bioorganic and medicinal chemistry (2021). DOI: 10.1016 / j.bmc.2021.116551
Provided by Hiroshima University
Citation: Simplified antibiotic can set the stage for antitumor treatments (2022, January 31) retrieved January 31, 2022 from https://medicalxpress.com/news/2022-01-antibiotic-stage-antitumor-treatments.html
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