WO2024144590A1 - Deltoin compound for use as anticancer agent - Google Patents
Deltoin compound for use as anticancer agentInfo
- Publication number
- WO2024144590A1 WO2024144590A1 PCT/TR2023/051306 TR2023051306W WO2024144590A1 WO 2024144590 A1 WO2024144590 A1 WO 2024144590A1 TR 2023051306 W TR2023051306 W TR 2023051306W WO 2024144590 A1 WO2024144590 A1 WO 2024144590A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- cancer
- cell
- cancers
- lymphoma
- carcinoma
- Prior art date
Links
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Abstract
The present invention relates to the use of deltoin drug substances obtained from natural sources as anticancer agents in cancer treatment and pharmaceutical compositions containing this agent.
Description
DELTOIN COMPOUND FOR USE AS ANTICANCER AGENT
Technical Field
The present invention relates to the use of deltoin drug substances obtained from natural sources as anticancer agents in cancer treatment and pharmaceutical compositions containing this agent.
State of the Art (Background)
The present invention relates to the field of cancer treatment, as mentioned. More specifically, it relates to the use of naturally derived chemotherapy agents for cancer treatment.
Cancer is a group of diseases characterized by uncontrolled growth and spread of abnormal cells. These cells can invade and damage nearby tissues and can also spread to other parts of the body through the bloodstream or lymphatic system. There are many different types of cancer, and they can occur almost anywhere in the body.
Chemotherapy is a widely preferred treatment option for cancer and involves the use of medications to terminate cancer cells. Chemotherapy is an effective way to destroy cancer cells and shrink tumors, but it also damages normal cells, leading to side effects such as nausea, vomiting, hair loss, and increased risk of infection. In addition, many cancer cells may become resistant to chemotherapy drugs during the treatment process, making it difficult to treat cancer effectively.
One way to improve my chemotherapy agents is to make them more selective so that they only target cancer cells and maintain normal cells as much as possible. Chemotherapy agents obtained from natural sources may have the potential to be more selective than synthetic chemotherapy drugs. These agents are derived from plants, animals, or other natural sources rather than being synthesized in a laboratory. Examples of chemotherapy agents obtained from natural sources include docetaxel, paclitaxel, vincristine, vinblastine, and semi-synthetic derivatives derived from the compounds isolated from Catharanthus roseus (rosette) and
Taxus baccata yew tree) plants such as 10-deacetylbaccatin III.
The use of chemotherapy agents obtained from natural sources for cancer treatment may offer several potential benefits compared to synthetic chemotherapy drugs. For example, these agents may be less toxic to normal cells and have other beneficial effects on the body. More research is needed to fully understand the potential of naturally obtained chemotherapy agents and identify the most effective ways to use them in cancer treatment.
Thus, it is an object of the present invention to provide a method for treating cancer using naturally derived chemotherapy agents. Another object of the present invention is to provide an agent suitable for use in cancer treatment.
Brief Description of the Invention
The inventors have developed pharmaceutical compositions comprising deltoin drug substance and optionally at least one pharmaceutically usable excipient for use as an anticancer agent in the treatment of cancer disease, considering the problems in state of the art described above.
Detailed Description of the Invention
The present invention relates to pharmaceutical compositions comprising deltoin as the drug substance and optionally at least one pharmaceutically acceptable excipient for use as a medicament in the treatment of cancer disease.
Deltoin drug substance (Formula I) is provided from plants belonging to the Apiaceae family.
Formula I
In their studies, the inventors have observed that the deltoin molecule has a toxic effect on various cancer cells. It has been determined by the studies conducted by the inventors that the toxic effect of the compound is extremely strong, especially in brain cancer cells, and that it has a close and selective effect on the effect of cisplatin used as a chemotherapy agent in the known state of the art. Although the deltoin molecule of the invention has a toxic effect as good as cisplatin on cancer cells, it surprisingly shows approximately 12 times less toxic effect than cisplatin on healthy cells. This shows that the deltoin molecule is effective on cancer and offers a much safer and more selective chemotherapy possibility compared to cisplatin, a known chemotherapy agent.
The fact that the deltoin molecule is a compound with a structure different from the classes of molecules used in cancer treatment so far, that it has a selective effect on various types of cancer such as brain cancer, that it has low toxicity on healthy cells and that it has a very high cytotoxic effect on cancer cells, for example at the micromolar dose level, distinguishes it from other chemotherapy agents existing in state of the art and makes it superior.
The cancer disease mentioned within the scope of the invention refers to carcinomas, melanomas, sarcomas, leukemias, lymphomas, germ cell tumors, brain and spinal cord cancers, or other types of cancer.
Depending on the region of occurrence, the cancers mentioned in the scope of the invention may be bone and muscle sarcomas, brain and nervous system cancers, breast cancers, endocrine system cancers, eye cancers, gastrointestinal cancers, genitourinary and gynecological cancers, head and neck cancers, hematopoietic cancers, skin cancers, breast and respiratory system cancers, HIV/AIDS-related cancers or epithelioid hemangioendothelioma (EHE), desmoplastic small round cell tumor, Liposarcoma.
The bone and muscle sarcomas mentioned within the scope of the invention may be chondrosarcoma, Ewing's sarcoma, malignant fibrous histiocytoma/osteosarcoma of the bone, osteosarcoma, rhabdomyosarcoma, leiomyosarcoma, myxosarcoma, fibrocartilaginous mesenchymoma of the bone.
The brain and nervous system cancers mentioned within the scope of the invention may be
astrocytoma, brainstem glioma, pilocytic astrocytoma, ependymoma, primitive neuroectodermal tumor, cerebellar astrocytoma, cerebral astrocytoma, glioblastoma, glioma, medulloblastoma, neuroblastoma, oligodendroglioma, pineal astrocytoma, pituitary adenoma, visual tract, and hypothalamic glioma.
The breast cancers mentioned within the scope of the invention may be breast cancer, inflammatory breast cancer, invasive lobular carcinoma, tubular carcinoma, invasive cribriform carcinoma of the breast (also called invasive cribriform carcinoma), medullary carcinoma, male breast cancer, phylloid tumor, breast secretory carcinoma, papillary carcinomas of the breast.
The endocrine system cancers mentioned within the scope of the invention may be adrenocortical carcinoma, islet cell carcinoma (endocrine pancreas), multiple endocrine neoplasia syndrome, parathyroid cancer, pheochromocytoma, thyroid cancer, and Merkel cell carcinoma.
The eye cancers mentioned within the scope of the invention may be uveal melanoma, retinoblastoma, and optic nerve glioma.
The gastrointestinal cancers mentioned within the scope of the invention may be anal cancer, appendix cancer, cholangiocarcinoma, carcinoid tumor, gastrointestinal, colon cancer, extrahepatic bile duct cancer, gallbladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), hepatocellular cancer, pancreas cancer, islet cell, rectum cancer, small intestine cancer.
The genitourinary and gynecological cancers mentioned within the scope of the invention may be bladder cancer, cervical cancer, endometrial cancer, extragonadal germ cell tumor, ovarian cancer, ovarian epithelial cancer (surface epithelial-stromal tumor), ovarian germ cell tumor, penile cancer, kidney cancer, renal cell carcinoma, renal pelvis and ureter, transition cell cancer, prostate cancer, testicular cancer, pregnancy trophoblastic tumor, ureter and renal pelvis, transition cell cancer, urethral cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Wilms' tumor (nephroblastoma).
The head and neck cancers mentioned within the scope of the invention may be esophageal
cancer, head and neck cancer, nasopharyngeal carcinoma, oral cancer, oropharyngeal cancer, paranasal sinus and nasal cavity cancer, pharyngeal cancer, salivary gland cancer, hypopharyngeal cancer.
Hematopoietic cancers mentioned within the scope of the invention may be: acute biphenotypic leukemia, acute eosinophilic leukemia, acute lymphoblastic leukemia, acute myeloid leukemia, acute myeloid dendritic cell leukemia, AIDS-related lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, B-cell prolymphocytic leukemia, Burkitt's lymphoma, chronic lymphocytic leukemia, chronic myelogenous leukemia, cutaneous T-cell lymphoma, diffuse large B-cell lymphoma, Follicular lymphoma, hairy cell leukemia, hepatosplenic T-cell lymphoma, Hodgkin's lymphoma, intravascular large B-cell lymphoma, large granular lymphocytic leukemia, lymphoplasmacytic lymphoma, lymphomatoid granulomatosis, mantle cell lymphoma, marginal zone B-cell lymphoma, mast cell leukemia, mediastinal large B-cell lymphoma, multiple myeloma/plasma cell neoplasm, myelodysplastic syndromes, mucosa-related lymphoid tissue lymphoma, mycosis fungoides, nodal marginal zone B-cell lymphoma, non-Hodgkin's lymphoma, precursor B lymphoblastic leukemia, primary central nervous system lymphoma, primary cutaneous follicular lymphoma, primary cutaneous immunocytoma, primary effusion lymphoma, plasmablastic lymphoma, Sezary syndrome, splenic marginal zone lymphoma, T-cell prolymphocytic leukemia.
The skin cancers mentioned within the scope of the invention can be basal cell carcinoma, squamous cell carcinoma, squamous cell skin cancer, skin adnexal tumors (e.g., sebaceous carcinoma), melanoma, Merkel cell carcinoma, keratoacanthoma, primary dermal sarcomas (e.g., dermatofibrosarcoma protuberans), primary cutaneous lymphomas (e.g., mycosis fungoides).
The breast and respiratory system cancers mentioned within the scope of the invention may be lung adenocarcinoma, bronchial adenomas/carcinoids, small cell lung cancer, mesothelioma, non-small cell lung cancer, non-small cell lung carcinoma, pleuropulmonary blastoma, laryngeal cancer, thymoma and thymic carcinoma, squamous cell carcinoma of the lung.
HIV/AIDS-related cancers mentioned within the scope of the invention can be AIDS-related
cancers, Kaposi's sarcoma.
The pharmaceutical compositions comprising the drug substance deltoin of the invention are for use in the treatment of at least one or some or all of the cancer diseases mentioned herein.
A preferred embodiment of the invention relates to the use of pharmaceutical compositions comprising deltoin as the drug substance and optionally at least one pharmaceutically acceptable excipient as a therapeutic agent in the treatment of brain and nervous system cancers such as astrocytoma, brainstem glioma, pilocytic astrocytoma, ependymoma, primitive neuroectodermal tumor, cerebellar astrocytoma, cerebral astrocytoma, glioblastoma, glioma, medulloblastoma, neuroblastoma, oligodendroglioma, pineal astrocytoma, pituitary adenoma, visual tract, and hypothalamic glioma.
In another aspect, the invention relates to pharmaceutical compositions containing deltoin as the drug substance. The compositions of the invention may comprise at least one pharmaceutically acceptable excipient in addition to deltoin. The excipient may be selected from substances well known in the pharmaceutical technology that do not have any therapeutic activity that would be useful in preparing the formulation, adjusting its bioavailability and/or release.
The pharmaceutical compositions, according to the invention, may be prepared in different pharmaceutical forms considering the physical condition of the patients, the type of disease, or similar conditions.
The terms "treatment" or "therapeutic activity" mentioned within the scope of the invention refer to the shortening of the treatment period, the acceleration of recovery, the disappearance of at least one symptom of the disease, the decrease of at least one symptom of the disease, the decrease in tumor size, the disappearance of the tumor, the decrease in the level of the relevant cancer marker or the disappearance of the cancer marker or the return of the cancer marker to a level within limits considered normal.
The expression "comprising" within the scope of the invention is also used in the sense of "including."
Applications of the invention may be combined where technically appropriate.
Claims
1. Pharmaceutical compositions comprising deltoin (Formula I) as the drug substance and optionally at least one pharmaceutically acceptable excipient for use as a medicament in the treatment of cancer disease.
Formula I
2. A pharmaceutical composition, according to Claim 1, is characterized in that the cancer disease includes bone and muscle sarcomas, brain and nervous system cancers, breast cancers, endocrine system cancers, eye cancers, gastrointestinal cancers, genitourinary and gynecological cancers, head and neck cancers, hematopoietic cancers, skin cancers, breast and respiratory system cancers, HIV/AIDS-related cancers or epithelioid hemangioendothelioma (EHE), desmoplastic small round cell tumor, liposarcoma.
3. A pharmaceutical composition, according to Claim 2, is characterized in that the bone and muscle sarcomas include chondrosarcoma, Ewing's sarcoma, malignant fibrous histiocytoma/osteosarcoma of the bone, osteosarcoma, rhabdomyosarcoma, leiomyosarcoma, myxosarcoma, fibrocartilaginous mesenchymoma of the bone.
4. A pharmaceutical composition, according to Claim 2, is characterized in that the brain and nervous system cancers include astrocytoma, brainstem glioma, pilocytic astrocytoma, ependymoma, primitive neuroectodermal tumor, cerebellar astrocytoma, cerebral astrocytoma, glioblastoma, glioma, medulloblastoma, neuroblastoma, oligodendroglioma, pineal astrocytoma, pituitary adenoma, visual tract, and hypothalamic glioma.
5. A pharmaceutical composition, according to Claim 2, is characterized in that the breast cancers include breast cancer, inflammatory breast cancer, invasive lobular carcinoma,
tubular carcinoma, invasive cribriform carcinoma of the breast (also called invasive cribriform carcinoma), medullary carcinoma, male breast cancer, phylloid tumor, breast secretory carcinoma, papillary carcinomas of the breast.
6. A pharmaceutical composition, according to Claim 2, is characterized in that the endocrine system cancers include adrenocortical carcinoma, islet cell carcinoma (endocrine pancreas), multiple endocrine neoplasia syndrome, parathyroid cancer, pheochromocytoma, thyroid cancer, and Merkel cell carcinoma.
7. A pharmaceutical composition, according to Claim 2, is characterized in that the eye cancers include uveal melanoma, retinoblastoma, and optic nerve glioma.
8. A pharmaceutical composition, according to Claim 2, is characterized in that the gastrointestinal cancers include anal cancer, appendix cancer, cholangiocarcinoma, carcinoid tumor, gastrointestinal, colon cancer, extrahepatic bile duct cancer, gallbladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), hepatocellular cancer, pancreas cancer, islet cell, rectum cancer, small intestine cancer.
9. A pharmaceutical composition, according to Claim 2, is characterized in that genitourinary and gynecological cancers include bladder cancer, cervical cancer, endometrial cancer, extragonadal germ cell tumor, ovarian cancer, ovarian epithelial cancer (surface epithelial- stromal tumor), ovarian germ cell tumor, penile cancer, kidney cancer, renal cell carcinoma, renal pelvis and ureter, transition cell cancer, prostate cancer, testicular cancer, pregnancy trophoblastic tumor, ureter and renal pelvis, transition cell cancer, urethral cancer, uterine sarcoma, vaginal cancer, vulvar cancer, Wilms' tumor (nephroblastoma).
10. A pharmaceutical composition, according to Claim 2, is characterized in that the head and neck cancers include esophageal cancers, head and neck cancers, nasopharyngeal carcinomas, oral cancers, oropharyngeal cancers, paranasal sinus and nasal cavity cancers, pharyngeal cancers, salivary gland cancers, hypopharyngeal cancers.
11. A pharmaceutical composition, according to Claim 2, is characterized in that hematopoietic cancers include acute biphenotypic leukemia, acute eosinophilic leukemia,
acute lymphoblastic leukemia, acute myeloid leukemia, acute myeloid dendritic cell leukemia, AIDS-related lymphoma, anaplastic large cell lymphoma, angioimmunoblastic T-cell lymphoma, B-cell prolymphocytic leukemia, Burkitt lymphoma, chronic lymphocytic leukemia, chronic myelogenous leukemia, cutaneous T-cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, hairy cell leukemia, hepatosplenic T- cell lymphoma, Hodgkin's lymphoma, intravascular large B-cell lymphoma, large granular lymphocytic leukemia, lymphoplasmacytic lymphoma, lymphomatoid granulomatosis, mantle cell lymphoma, marginal zone B-cell lymphoma, mast cell leukemia, mediastinal large B-cell lymphoma, multiple myeloma/plasma cell neoplasm, myelodysplastic syndromes, mucosa-related lymphoid tissue lymphoma, mycosis fungoides, nodal marginal zone B-cell lymphoma, non-Hodgkin lymphoma, precursor B lymphoblastic leukemia, primary central nervous system lymphoma, primary cutaneous follicular lymphoma, primary cutaneous immunocytoma, primary effusion lymphoma, plasmablastic lymphoma, Sezary syndrome, splenic marginal zone lymphoma, T-cell prolymphocytic leukemia.
12. A pharmaceutical composition, according to Claim 2, is characterized in that the skin cancers include basal cell carcinoma, squamous cell carcinoma, squamous cell skin cancer, skin adnexal tumors (e.g., sebaceous carcinoma), melanoma, Merkel cell carcinoma, keratoacanthoma, primary dermal sarcomas (e.g., dermatofibrosarcoma protuberans), primary cutaneous lymphomas (e.g., mycosis fungoides).
13. A pharmaceutical composition, according to Claim 2, is characterized in that the breast and respiratory system cancers include lung adenocarcinoma, bronchial adenomas/carcinoids, small cell lung cancer, mesothelioma, non-small cell lung cancer, non-small cell lung carcinoma, pleuropulmonary blastoma, laryngeal cancer, thymoma and thymic carcinoma, squamous cell carcinoma of the lung.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| TR2022/021304 | 2022-12-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2024144590A1 true WO2024144590A1 (en) | 2024-07-04 |
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