PharmD Lecture 9: Alkaloids in Phytochemistry

Here are the study notes in detailed bullet points, focusing on key facts with context:

Quinoline Alkaloids to Steroidal Alkaloids

• Alkaloids are categorized into several types, including Quinoline, Isoquinoline, Indole, β-Carboline, Imidazole, Purine, Terpenoid, Pyridine, Piperidine, Pyrrolizidine, Quinolizidine, Steroidal, Tropane/Ecgonine, and Marine Alkaloids.

Terpenoid Alkaloids

• Terpenoid Alkaloids are derived from the isoprenoid pathway and can be classified into monoterpenoids (C10), sesquiterpenoids (C15), diterpenoids (C20), and triterpenoids (C30).
• Paclitaxel (Taxol) is a diterpene alkaloid obtained from the Pacific Yew tree (Taxus brevifolia).
• Paclitaxel is used to treat ovarian and breast cancer and is administered via I.V. infusion.
• The mechanism of action of Paclitaxel involves binding to the β-subunit of tubulin, stabilizing microtubules, and inducing apoptosis.

Structure Activity Relationship (SAR) of Taxol

• The SAR of Taxol involves modifying the side chain and taxane nucleus to simplify synthetic studies and create more active analogues.
• Modifications to the side chain include changing the C-2' and C-3' positions, while modifications to the taxane nucleus involve changes to the C-7, C-10, and oxetane ring positions.

Related Compounds of Pharmaceutical Importance

• Taxotere is a water-soluble, semi-synthetic derivative of Taxol used to treat ovarian and breast cancer.
• 10-Deacetylbaccatin III and Baccatin III are obtained from tissue cultures of Taxus baccata and used as starting materials for semi-synthetic Taxol and Taxotere.

Steroidal Alkaloids

• Steroidal Alkaloids are based on a C-27 cholestane skeleton and are nitrogen analogues of steroidal saponins.
• They occur in glycosidal combination with sugars and are found in Solanum and Veratrum species.

Solanum Alkaloids

• Solanine and Solasonine are two major steroidal glycoalkaloids found in Solanum species.
• Solanine contains solanidine as the aglycone and solanose as the sugar part.
• Solasonine contains solasodine as the aglycone and solanose as the sugar part.
• Solanidine is used as a starting material for the synthesis of steroidal drugs, while Solasonine is used as an agricultural insecticide and as a starting material for the synthesis of sexual hormones and corticosteroids.

Marine Alkaloids

• Marine Alkaloids are obtained from marine organisms and are known for their cytotoxic, antiviral, antimicrobial, insecticidal, and fungicidal activities.
• Examples of Marine Alkaloids include Pyridoacridines, Pyrroloacridines, Manzamines, and Indoles.### Marine Alkaloids
• Alkaloids are derived from marine organisms.

Indoles

• Dragmacidin: an alkaloid from the deep-water Caribbean sponge Dragmacidon sp.
• Inhibits growth of several cancer cell lines.
• Chemical structure: 5,6-Dibromo-tryptamine.

Pyrroles

• A tetrabromo-pyrrole was isolated from a purple-colored bacterium of the genus Alteromonas.
• Displays moderate antimicrobial activity.
• Chemical structure: Tetrabromo-pyrrole.
• 4,5-Dibromopyrrole-2-carboxylic acid: shows in vitro immunosuppressive activity.

Manzamines

• A unique class of β-carboline marine alkaloids with an unusual tetra- or pentacyclic system.
• Exhibits a variety of bioactivities against:
• Infectious diseases.
• Cancer.
• Inflammatory diseases.
• Manzamine A:
• A cytotoxic compound.
• Shows great potential against malaria, with improved potency relative to chloroquine and artemisinin.