F1 Antineoplastic Agents Lecture Flashcards

Flashcards covering terms, drug classes, mechanisms, and specific agents for antineoplastic therapy based on medicinal organic chemistry lecture notes.

Neoplasms

New or unusual growth of tissue, also known as tumors.

Benign

A type of growth that is encapsulated and does not invade local tissues or spread.

Malignant

A characteristic of cancer cells representing the ability to invade local tissues and spread to other sites.

Carcinomas

A type of cancer originating from epithelial cells.

Sarcoma

A type of cancer originating from connective tissues.

Lymphoma

A hematologic malignancy originating in the lymphatic system.

Leukemia

A hematologic malignancy originating from blood-forming elements.

Angiogenesis

The development and formation of new blood vessels, often associated with tumor growth.

Initiation

The first step in carcinogenesis triggered by causes such as chemicals, viruses, or radiation.

Promotion

The stage of carcinogenesis following initiation that leads to progression and malignant neoplasm.

Progression

The final stage of carcinogenesis leading to the development of a malignant neoplasm (cancer).

Curative Treatment

Treatment aimed at the total eradication of cancer cells to a level where host immunological defenses can control them.

Palliative Treatment

Treatment focused on the alleviation of symptoms, decreasing tumor size, and increasing survival while improving quality of life.

Adjuvant therapy

The attempt to eradicate microscopic cancer following surgery.

Salvage Chemotherapy

An attempt to get a patient into remission after previous therapies have failed.

NeoAdjuvant Chemotherapy

Chemotherapy given to decrease the tumor burden before definitive therapy such as surgery or radiation.

Log Kill Hypothesis

According to this hypothesis, chemotherapeutic agents kill a constant fraction of cells (first order kinetics) rather than a specific number of cells after each dose.

Physical Detection Threshold

The smallest physically detectable tumor burden, which is $10^9$ cells, weighing about $1\,g$ or the size of a small grape.

$G_0$ phase

The resting phase of the tumor cell cycle.

$G_1$ phase

The cell cycle phase of early protein synthesis and synthesis of cellular components needed for DNA synthesis.

$S$ phase

The phase of the cell cycle dedicated to DNA synthesis and the replication of the DNA genome.

$G_2$ phase

The cell cycle phase characterized by RNA synthesis, growth, and preparation for mitosis, including a DNA check.

$M$ phase

The mitosis phase where cell division, cell differentiation, and physical separation occur.

L-asparaginase

A drug with unique action specifically in the $G_1$ phase by inhibiting L-asparagine, a nutrient for tumor cells.

Antimetabolites

A drug class that acts mainly in the $S$ phase by mimicking DNA building blocks.

Bleomycin

A cytotoxic antibiotic that acts in the $G_2$ phase by causing DNA strand breaks.

Vinca Alkaloids

A class of plant products, including Vincristine and Vinblastine, that target the $M$ phase by disrupting the spindles that pull chromosomes apart.

Alkylating Agents MOA

Replacement of a hydrogen ion in an atom with an alkyl group, leading to the inhibition of DNA replication and cell death.

Mechlorethamine

A di-alkylating nitrogen mustard used for Hodgkin’s lymphoma and mycosis fungoides.

Cyclophosphamide

A cell cycle-nonspecific nitrogen mustard used for breast cancer, lymphoma, and various sarcomas.

Ifosfamide

A nitrogen mustard used as third-line therapy in the treatment of testicular cancer.

Melphalan (Alkeran)

A nitrogen mustard available in $2\,mg$ tablets or $50\,mg$ IV, often used in bone marrow transplants for multiple myeloma.

Chlorambucil (Leukeran)

A nitrogen mustard used for Hodgkin’s lymphoma and chronic lymphocytic leukemia, typically administered with prednisone.

MESNA

An agent used to detoxify the byproduct Acrolein produced by cyclophosphamide and ifosfamide.

Acrolein

A toxic metabolite of cyclophosphamide and ifosfamide that causes hemorrhagic cystitis.

Thiotepa (Thioplex)

An ethyleneimine used for bladder, ovarian, and breast cancer, with dose-limiting myelosuppression.

Busulfan (Myleran)

An alkyl sulfonate containing two sulfonate leaving groups joined by a four-carbon chain, used for chronic myelogenous leukemia (CML).

Busulfan Lung

A phrase referring to interstitial pulmonary fibrosis, a pulmonary adverse symptom of treatment with busulfan.

Nitrosoureas

A class of alkylating agents that undergo spontaneous non-enzymatic degradation to form the $2\text{-chloroethyl carbonium ion}$, including Carmustine and Lomustine.

$$2\text{-chloroethyl carbonium ion}$$

The active alkylating agent formed from the degradation of nitrosoureas.

Isocyanate

A compound liberated by nitrosoureas that attaches carbamoyl groups to proteins, inactivating DNA.

Carmustine (BCNU)

A bis-chloroethyl nitrosourea often used as a sterile implant known as a GLIADEL Wafer ($7.7\,mg$ carmustine/wafer).

Lomustine (CCNU)

A chloroethyl-cyclohexyl nitrosourea used for primary and metastatic brain cancers and Hodgkin’s lymphoma.

Streptozocin

A nitrosourea with a glucose moiety that targets the $\beta\text{-cells}$ of the pancreas, used for islet cell carcinoma.

Dacarbazine

A triazene that acts as an alkylating agent following CYP-mediated activation and the formation of $CH_2N_2$ (diazomethane).

Procarbazine

An antineoplastic triazene originally developed as a monoamine oxidase inhibitor.

Antimetabolites Dose-Limiting Toxicity

Myelosuppression is the dose-limiting toxicity for all drugs in this class.

6-Mercaptopurine ($6-MP$)

The thiol analog of hypoxanthine that requires bioactivation by the enzyme HGPRT.

TPMT

$\text{Thiopurine-S-methyl transferase}$, the enzyme responsible for the metabolic inactivation of $6-MP$ via S-Methylation.

Xanthine Oxidase ($XO$)

An enzyme that inactivates $6-MP$ through oxidation, leading to the formation of thiouric acid.

6-thioinosinate ($6-MPMP$)

The active ribonucleotide metabolite formed from the bioactivation of $6-Mercaptopurine$.

HGPRT

The enzyme required to bioactivate $6-Mercaptopurine$ to its active form, $6-thioinosinate$.

Azathioprine

A derivative of $6-Mercaptopurine$ used primarily as an immunosuppressive agent.

5-Fluorouracil ($5-FU$)

A pyrimidine drug that acts as a thymidylate synthase inhibitor and is the first choice for colon cancer treatment.

FdUMP

$\text{Fluorodeoxyuridine monophosphate}$, the 'fraudulent' nucleotide formed from $5-FU$ that inhibits thymidylate synthetase.

Thymidylate Synthase

An enzyme important in the synthesis of pyrimidine for DNA replication; the principal target of $5-FU$.

Capecitabine (Xeloda)

A pyrimidine prodrug of $5-Fluorouracil$ ($5-FU$).

Tegafur

A pyrimidine derivative that serves as a prodrug of $5-Fluorouracil$ ($5-FU$).

Cytarabine ($Ara-C$)

An antimetabolite ($1\beta\text{-arabinofuranosylcytosine}$) converted into a triphosphate that damages DNA during the $S$ phase.

Gemcitabine

A pyrimidine analogue used as a first-line treatment for small lung cancer that replaces cytidine during DNA replication.

Methotrexate ($MTX$)

A folic acid analog that blocks DNA synthesis by inhibiting the enzyme dihydrofolate reductase.

Dihydrofolate Reductase

The enzyme inhibited by Methotrexate to block the synthesis of DNA.

Leucovorin

A compound given $6\text{-}24\,hrs$ after $MTX$ administration to prevent toxicity in normal cells.

Intercalation

A mechanism of action where a planar molecule inserts itself between base pairs of DNA, inhibiting Topoisomerase.

Dactinomycin

A cytotoxic antibiotic isolated from $Streptomyces parvulus$ that intercalates between G-C base pairs.

Phenoxazone

The chromophore common to the group of actinomycin compounds, including Dactinomycin.

Anthracyclines

Cytotoxic antibiotics, like Daunorubicin and Doxorubicin, characterized by a planar oxidized anthracene nucleus fused to a cyclohexane ring.

Mitoxantrone

An intercalator that inhibits Topoisomerase II and exhibits reduced cardiotoxicity compared to anthracyclines.

Epipodophyllotoxins

Semisynthetic derivatives of podophyllotoxin, such as Etoposide and Teniposide, which inhibit microtubule function or topoisomerase.

Etoposide

An epipodophyllotoxin that forms a ternary complex with Topoisomerase II and DNA, causing strand breakage.

Teniposide

An epipodophyllotoxin containing a thiophene group that makes it 10 times more potent than Etoposide.

Camptothecins

Type I Topoisomerase inhibitors, such as Topotecan and Irinotecan, extracted from a Chinese tree.

$$Camptotheca accuminata$$

The Chinese tree from which camptothecin agents are extracted.

Periwinkle

The plant source of Vinca Alkaloids such as Vincristine and Vinblastine.

Catharanthine and Vindoline

The two moieties that compose the structure of Vinca Alkaloids.

Taxanes

Plant products first isolated from the bark of the Western or Pacific yew ($Taxus brevifolia$) that bind to the middle of the $\beta\text{-tubulin}$ subunit.

Cisplatin

The original platinum-containing complex, known as cis-dichlorodiammineplatinum II, which inhibits DNA polymerase.

Carboplatin

A cis-isomer platinum complex containing a cyclobutane dicarboxylate ligand.

Oxaliplatin

A platinum agent containing an oxalate ligand and $1,2\text{-diaminocyclohexane}$.

Ormaplatin

A platinum agent containing six ligands, including four chlorides and $1,2\text{-diaminocyclohexane}$.

Arsenic Trioxide

An antineoplastic used for promyelocytic leukemia whose active form is dimethyl arsenic acid.

Hydroxyurea

An agent active in the $S$ phase that inhibits the conversion of ribonucleotides to deoxyribonucleotides by complexing with iron.

Guanazole

An agent with the same action as hydroxyurea, with the active form being diaminotriazole.

Pegaspargase

A form of L-asparaginase formulated with polymeric monomethoxypropylene glycol.

Mitotane

A cytotoxic agent selective only for the adrenal cortex of the adrenal gland.