Epoxy-guaiane derivatives and treatment of cancer
Inventors
Beutler, John A. • Ratnayake, Ranjala • Covell, David • Johnson, Tanya R.
Assignees
US Department of Health and Human Services
Publication Number
US-8410292-B2
Publication Date
2013-04-02
Expiration Date
2028-12-30
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
Disclosed are englerins and derivatives (I) thereof useful in the treatment of a number of cancers, particularly renal cancer, as well as pharmaceutical compositions and method of treating a patient with the use of these derivatives. The englerins, for example Englerin A and Englerin B, can be isolated from the plant Phyllanthus engleri or produced by synthetic methods. An example of the englerin derivative is 2′-chloroenglerin A, which has the structure (II), wherein double bond ‘a’ is E, Z, or a mixture of E and Z.
Core Innovation
The invention provides isolated or purified englerin compounds and derivatives thereof, useful in treating various cancers, particularly renal cancer. These compounds include Englerin A and Englerin B, which can be isolated from the plant Phyllanthus engleri or produced synthetically. The invention also includes pharmaceutical compositions comprising these compounds and methods of treating patients with these derivatives.
The invention discloses compounds of formula (I), or epimers thereof, featuring specific substituents such as aryl groups (optionally substituted), and variations in bonds and functional groups described by variables including Ar, X, R1, R2, R3, R4, R5, R6, and double bond ‘a’. These differences provide a series of englerin derivatives with potential selective anticancer activity.
The problem addressed by the invention is the need for new cancer treatments, especially targeting renal cancer. Given the high morbidity and mortality rates of renal cancer and the traditional medicinal use of various Phyllanthus species, the invention seeks to isolate or synthesize compounds that demonstrate anticancer effects, specifically inhibiting growth of renal and other cancer cell lines.
Claims Coverage
The independent claims cover isolated or purified englerin compounds of specified formulas, pharmaceutical compositions containing these compounds, and methods of treating cancer using these compounds.
Isolated or purified englerin compounds
An isolated or purified compound defined by a specific chemical formula, including Englerin A and Englerin B, characterized by particular structural features including aryl groups, variations in bond types, and functional groups as described in the specification.
Compound of formula (I) and epimers
A compound or epimer having formula (I) with defined substituents including Ar as an optionally substituted aryl group, X as O, NH, or S, and specific groups R1 through R6, with variants in bond types and substituents, enabling diverse englerin derivatives.
Pharmaceutical composition containing englerin compounds
A pharmaceutical composition comprising a pharmaceutically acceptable carrier combined with an englerin compound as claimed in the previous claims.
Method of treating cancer using englerin compounds
A method of treating cancer in an animal by administering an effective amount of an englerin compound as claimed in the patent, including treatment of various cancers such as renal cancer.
The claims collectively encompass engineered compounds derived from englerins, pharmaceutical formulations containing them, and their therapeutic application for treating cancers, particularly renal cancer, emphasizing specific structural features and treatment methodologies.
Stated Advantages
Englerin compounds, including derivatives, demonstrate selective activity against renal cancer and other cancer cell lines, with effectiveness at low micromolar or nanomolar concentrations.
The invention provides highly potent compounds with significant growth inhibition of cancer cell lines, enabling therapeutic effects in cancer treatments.
The compounds can be isolated from natural sources or prepared synthetically, allowing flexibility in production methods.
Pharmaceutical formulations can be prepared in various acceptable forms and carriers, allowing diverse administration routes such as oral, parenteral, topical, aerosol, and suppository.
Documented Applications
Treatment of various cancers including renal cancer, leukemia, non-small cell lung cancer, colon cancer, melanoma, prostate cancer, breast cancer, CNS cancer, and ovarian cancer.
Use in pharmaceutical compositions for administration via oral, parenteral (intravenous, intraarterial, subcutaneous, etc.), topical, aerosol/inhalation, rectal, and vaginal routes.
Interested in licensing this patent?