Antibiotics, Plant products, Miscellaneous.pptx

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1. Antibiotics, Plant products, Miscellaneous (Antineoplastic agents) B Y : N.SRILAKSHMI Assistant Professor KL COLLEGE OF PHARAMCY KLEF VADDESWARAM Medicinal chemistry -II

2. Antibiotics Anti-neoplastic agents:

3. Dactinomycin The structure of phenoxazine consists of an oxazine fused to two benzene rings. It occurs as the central core of a number of naturally occurring chemical compounds such as dactinomycin and litmus. The dyes Nile blue and Nile red are also based on a phenoxazine core. Phenoxazine IUPAC : 2-amino-4,6-dimethyl-3-oxo-1- N ,9- N -bis pentapeptide lactone carboxylic acid phenoxazine Pentapeptide lactone Pentapeptide lactone

4. A compound composed of a two cyclic peptides attached to a phenoxazine that is derived from streptomyces parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy Ref: https://go.drugbank.com/drugs/DB00970 https://medlineplus.gov/druginfo/meds/a682224.html Synonyms: A ctinomycin D DACTINOMYCIN Actinomycin C1 Actinomycin IV Cosmegen

5. Daunorubicin Tetracene Daunorubicin is an anthracycline antineoplastic antibiotic with therapeutic effects similar to those of  doxorubicin . Daunorubicin exhibits cytotoxic activity through topoisomerase-mediated interaction with DNA, thereby inhibiting DNA replication and repair and RNA and protein

6. Properties and uses: Daunorubicin is obtained from the fermentation of Streptomyces peuletieues . This drug bind to the DNA and inhibit nucleic acid synthesis, mitosis, and promote chromosomal aberration. These drugs are used for the treatment of acute myclocytic leukaemia, primary hepatocellular carcinomal , and ovarian endometrial carcinoma Daunorubicin is a natural product found in Actinomadura roseola. It has a role as an antineoplastic agent and a bacterial metabolite. It is an anthracycline, a member of tetracenequinones , a member of p-quinones and an aminoglycoside antibiotic. It is a conjugate base of a daunorubicin(1+). It derives from a  hydride  of a  tetracene . References: https://pubchem.ncbi.nlm.nih.gov/compound/Daunorubicin#section=3D-Conformer https://go.drugbank.com/drugs/DB00694 https://www.webmd.com/drugs/2/drug-5021/daunorubicin-intravenous/details A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of leukemia and other neoplasms.

7. Doxorubicin Doxorubicin is  a type of chemotherapy drug called an anthracycline . It slows or stops the growth of cancer cells by blocking an enzyme called topo isomerase 2. Cancer cells need this enzyme to divide and grow. You might have doxorubicin in combination with other chemotherapy drugs.

8. Properties and uses: Doxorubicin hydrochloride is an orange-red crystalline hygroscopic powder, soluble in water, and slightly soluble in methanol. Doxorubicin is 14-hydroxy daunoruibicin obtained from the cultures of Streptomyces peuletiues . It is one of the most effective antitumour agent. It is used in the treatment of acute lymphocytic leukaemia, breast, lung, ovarian, thyroid, gastric carcinoma, and Hodgkin’s disease. Dosage forms: Doxorubicin HCl injection I.P., Doxorubicin HCl tablets I.P., Doxorubicin injection B.P Ref: https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/doxorubicin#:~:text=Doxorubicin%20is%20a%20type%20of,combination%20with%20other%20chemotherapy%20drugs https://medlineplus.gov/druginfo/meds/a682221.html

9. Plant Products Anti-neoplastic agents:

10. Etoposide Etoposide is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug.  This medication is classified as a "plant alkaloid" and "topoisomerase II inhibitor."  Topoisomerase inhibitors (such as etoposide) are drugs that interfere with the action of topoisomerase enzymes (topoisomerase I and II). Topoisomerase enzymes control the manipulation of the structure of DNA necessary for replication.

11. A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. https://go.drugbank.com/drugs/DB00773 https://en.wikipedia.org/wiki/Etoposide https://chemocare.com/chemotherapy/drug-info/etoposide.aspx https://medlineplus.gov/druginfo/meds/a684055.html

12. Vincristin sulphate https://www.webmd.com/drugs/2/drug-7423/vincristine-intravenous/details https://theindianpharma.com/vincristine/ Vincristine sulphate is an anti-cancer medication indicated in acute lymphocytic leukemia , acute myeloid leukemia , Hodgkin’s disease, Non–Hodgkin’s malignant lymphomas (NHL), neuroblastoma, Wilms’ tumour, rhabdomyosarcoma and small cell lung cancer.

13. Mode of action: It binds to microtubular protein tubulin, prevents polymerization and assembly of microtubules, and causes mitotic spindle destruction. The chromosomes fail to move apart during mitosis and lead to metaphase arrest. Properties and uses: Vinca alkaloids are isolated from Catharanthus roseus. They have complex structures composed of a dimeric indole-containing moiety named catharanthine and an indoline -containing moiety named vindoline. Four closely related compounds have antitumour activity, that is, vincristine, vinblastine, vinrosidine , and vinleurosine . Semisynthetic derivative vinorelbine is also used as an antitumour agent.

14. Vinblastin sulphate Vinblastine is used in combination with other chemotherapy drugs to treat Hodgkin's lymphoma (Hodgkin's disease) and non-Hodgkin's lymphoma (types of cancer that begin in a type of white blood cell that normally fights infection), and cancer of the testicles. It is also used to treat Langerhans cell histiocytosis (histiocytosis X; Letterer- Siwe disease; a condition in which too many of a certain type of white blood cell grows in parts of the body).  The antitumor activity of vinblastine is thought to be due primarily to inhibition of mitosis at metaphase through its interaction with tubulin. Vinblastine binds to the microtubular proteins of the mitotic spindle, leading to crystallization of the microtubule and mitotic arrest or cell death.

15. Mode of action: It binds to microtubular protein tubulin, prevents polymerization and assembly of microtubules, and causes mitotic spindle destruction. The chromosomes fail to move apart during mitosis and lead to metaphase arrest. Properties and uses: Vinca alkaloids are isolated from Catharanthus roseus. They have complex structures composed of a dimeric indole-containing moiety named catharanthine and an indoline -containing moiety named vindoline. Four closely related compounds have antitumour activity, that is, vincristine, vinblastine, vinrosidine , and vinleurosine . Semisynthetic derivative vinorelbine is also used as an antitumour agent. Refe : https://medlineplus.gov/druginfo/meds/a682848.html https://www.webmd.com/drugs/2/drug-52/vinblastine-intravenous/details

16. Miscellaneous Anti-neoplastic agents:

17. Mitotane Properties and uses: It is indicated only for treating adrenal cortex carcinoma. 1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene A derivative of the insecticide dichlorodiphenyldichloroethane that specifically inhibits cells of the adrenal cortex and their production of hormones. It is used to treat adrenocortical tumors and causes CNS damage, but no bone marrow depression. Ref: https://go.drugbank.com/drugs/DB00648 https://drugs.ncats.io/drug/78E4J5IB5J

18. Cisplatin Cisplatin is the square planar coordination complex  cis-[Pt(NH 3 ) 2 Cl 2 ] . The prefix cis indicates the cis isomer in which two similar ligands are in adjacent positions. Cisplatin, cisplatinum or cis- diamminedichloroplatinum (II) (CDDP) is a platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas and germ cell tumors. It was the first member of its class, which now also includes carboplatin and oxaliplatin

19. Properties and uses: Cisplatin is a yellow powder or yellow or orange-yellow crystals, slightly soluble in water, sparingly soluble in dimethylformamide, and practically insoluble in alcohol, used in testicular tumour. Dosage forms: Cisplatin injection B.P. https://go.drugbank.com/drugs/DB00515 https://www.researchgate.net/figure/Molecular-structure-of-cisplatin-This-platinum-compound-is-centered-around-two_fig1_333173986