Harmaline is a fluorescent psychoactive indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is a partially hydrogenated form of harmine. Harmaline is produced by various plants including Peganum harmala aswell as Banisteriopsis caapi. Harmaline has been investigated as an anti-cancer agent and for the treatment of dementia in rats. However, Harmaline is known to induce tremors in rats.

Altretamine is structurally similar to the alkylating agent triethylenemelamine (tretamine). Although Altretamine structurally resembles an alkylating agent, it has not been found to have alkylating activity in vitro. The precise mechanism of Altretamine cytotoxicity is unknown, although several proposals have been made. Altretamine requires N-demethylation in the liver to produce reactive intermediates (formaldehyde and/or iminium species) which covalently bind to DNA, resulting in DNA damage, or act as alkylating agents. Altretamine is used as a palliative treatment for persistent or recurrent ovarian cancer following treatment failure with a cisplatin- or alkylating agent-based combination. Side effects of Altretamine include nausea and vomiting, neurotoxicity (mood disorders, disorders of consciousness, ataxia, dizziness, vertigo), mild to moderate dose-related myelosuppression. Altretamine has been shown to be embryotoxic and teratogenic in rats and rabbits and may cause fetal damage when administered to a pregnant woman. Under the trade name Hexalen, Altretamine, is an antineoplastic agent. It is indicated for use as a single agent in the palliative treatment of patients with persistent or recurrent ovarian cancer following first-line therapy with a cisplatin and/or alkylating agent-based combination.

Clofazimine (Lamprene®) is a fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine (Lamprene®) exerts a slow bactericidal effect on Mycobacterium leprae (Hansen’s bacillus). It inhibits mycobacterial growth and binds preferentially to mycobacterial DNA. It also exerts anti-inflammatory properties in controlling erythema nodosum leprosum reactions. However, its precise mechanisms of action are unknown.

Streptozotocin (Streptozocin, STZ, Zanosar) is a naturally occurring chemical that is particularly toxic to the insulin-producing beta cells of the pancreas in mammals. It is used in medicine for treating certain cancers of the Islets of Langerhans and used in medical research to produce an animal model for hyperglycemia in a large dose as well as Type 1 diabetes with multiple low doses. Streptozocin inhibits DNA synthesis in bacterial and mammalian cells. In bacterial cells, a specific interaction with cytosine moieties leads to degradation of DNA. The biochemical mechanism leading to mammalian cell death has not been definitely established; streptozocin inhibits cell proliferation at a considerably lower level than that needed to inhibit precursor incorporation into DNA or to inhibit several of the enzymes involved in DNA synthesis. Although streptozocin inhibits the progression of cells into mitosis, no specific phase of the cell cycle is particularly sensitive to its lethal effects. Streptozocin is active in the L1210 leukemic mouse over a fairly wide range of parenteral dosage schedules. In experiments in many animal species, streptozocin induced a diabetes that resembles human hyperglycemic nonketotic diabetes mellitus. This phenomenon, which has been extensively studied, appears to be mediated through a lowering of beta cell nicotinamide adenine dinucleotide (NAD) and consequent histopathologic alteration of pancreatic islet beta cells. The metabolism and the chemical dissociation of streptozocin that occurs under physiologic conditions has not been extensively studied. When administered intravenously to a variety of experimental animals, streptozocin disappears from the blood very rapidly. In all species tested, it was found to concentrate in the liver and kidney. As much as 20% of the drug (or metabolites containing an N-nitrosourea group) is metabolized and/or excreted by the kidney. Metabolic products have not yet been identified.

Niclosamide is an antihelminth used against tapeworm infections. It may act by the uncoupling of the electron transport chain to ATP synthase. The disturbance of this crucial metabolic pathway prevents creation of adenosine tri-phosphate (ATP), an essential molecule that supplies energy for metabolism. Niclosamide works by killing tapeworms on contact. Adult worms (but not ova) are rapidly killed, presumably due to uncoupling of oxidative phosphorylation or stimulation of ATPase activity. The killed worms are then passed in the stool or sometimes destroyed in the intestine. Niclosamide may work as a molluscicide by binding to and damaging DNA. Niclosamide is used for the treatment of tapeworm and intestinal fluke infections: Taenia saginata (Beef Tapeworm), Taenia solium (Pork Tapeworm), Diphyllobothrium latum (Fish Tapeworm), Fasciolopsis buski (large intestinal fluke). Niclosamide is also used as a molluscicide in the control of schistosomiasis. Niclosamide was marketed under the trade name Niclocide, now discontinued.

Oxamniquine is an anthelmintic with schistosomicidal activity against Schistosoma mansoni, but not against other Schistosoma spp. Oxamniquine is a potent single-dose agent for treatment of S. mansoni infection in man, and it causes worms to shift from the mesenteric veins to the liver, where the male worms are retained; the female worms return to the mesentery, but can no longer release eggs. Oxamniquine is a semisynthetic tetrahydroquinoline and possibly acts by DNA binding, resulting in contraction and paralysis of the worms and eventual detachment from terminal venules in the mesentry, and death. Its biochemical mechanisms are hypothesized to be related to an anticholinergic effect, which increases the parasite’s motility, as well as to synthesis inhibition of nucleic acids. Oxamniquine acts mainly on male worms, but also induces small changes on a small proportion of females. Like praziquantel, it promotes more severe damage of the dorsal tegument than of the ventral surface. The drug causes the male worms to shift from the mesenteric circulation to the liver, where the cellular host response causes its final elimination. The changes caused in the females are reversible and are due primarily to the discontinued male stimulation rather than the direct effect of oxamniquine

Plicamycin (INN, also known as mithramycin; trade name Mithracin) is an antineoplastic antibiotic produced by Streptomyces plicatus. Plicamycin belongs to the group of medicines known as antineoplastics. It may be used to treat certain types of cancer. It is also used to treat hypercalcemia or hypercalciuria (too much calcium in the blood or urine) that may occur with some types of cancer. Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, plicamycin is used in certain patients with the following medical condition:Paget's disease of the bone. The manufacturer discontinued plicamycin in 2000. Several different structures are currently reported in different places all with the same chromomycin core, but with different stereochemistry in the glycoside chain, a 1999 study has re-investigated the compound and proposed a revised structure. Although the exact mechanism by which Mithracin (plicamycin) causes tumor inhibition is not yet known, studies have indicated that this compound forms a complex with deoxyribonucleic acid (DNA) and inhibits cellular ribonucleic acid (RNA) and enzymic RNA synthesis. The binding of Mithracin (plicamycin) to DNA in the presence of Mg + + (or other divalent cations) is responsible for the inhibition of DNA-dependent or DNA-directed RNA synthesis. This action presumably accounts for the biological properties of Mithracin (plicamycin). Plicamycin may also lower calcium serum levels by inhibiting the effect of parathyroid hormone upon osteoclasts or by blocking the hypercalcemic action of pharmacologic doses of vitamin D.

Pipobroman (trade names Vercite, Vercyte) is an anti-cancer drug that probably acts as an alkylating agent. It is marketed by Abbott Laboratories. Pipobroman (PB) has well documented clinical activity in polycythemia vera (PV) and essential thrombocythemia (ET). The mechanism of action is uncertain but pipobroman is thought to alkylate DNA leading to disruption of DNA synthesis and eventual cell death

Thioguanine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute nonlymphocytic leukemia. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. Thioguanine was first synthesized and entered into clinical trial more than 30 years ago. It is a 6-thiopurine analogue of the naturally occurring purine bases hypoxanthine and guanine. Intracellular activation results in incorporation into DNA as a false purine base. An additional cytotoxic effect is related to its incorporation into RNA. Thioguanine is cross-resistant with mercaptopurine. Cytotoxicity is cell cycle phase-specific (S-phase). Thioguanine competes with hypoxanthine and guanine for the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRTase) and is itself converted to 6-thioguanilyic acid (TGMP), which reaches high intracellular concentrations at therapeutic doses. TGMP interferes with the synthesis of guanine nucleotides by its inhibition of purine biosynthesis by pseudofeedback inhibition of glutamine-5-phosphoribosylpyrophosphate amidotransferase, the first enzyme unique to the de novo pathway of purine ribonucleotide synthesis. TGMP also inhibits the conversion of inosinic acid (IMP) to xanthylic acid (XMP) by competition for the enzyme IMP dehydrogenase. Thioguanine nucleotides are incorporated into both the DNA and the RNA by phosphodiester linkages, and some studies have shown that incorporation of such false bases contributes to the cytotoxicity of thioguanine. Its tumor inhibitory properties may be due to one or more of its effects on feedback inhibition of de novo purine synthesis; inhibition of purine nucleotide interconversions; or incorporation into the DNA and RNA. The overall result of its action is a sequential blockade of the utilization and synthesis of the purine nucleotides. Thioguanine is used for remission induction and remission consolidation treatment of acute nonlymphocytic leukemias. It is marketed under the trade name Lanvis and Tabloid among others.

Trioxsalen (trimethylpsoralen, trioxysalen or trisoralen) is a furanocoumarin and a psoralen derivative. It is obtained from several plants, mainly Psoralea corylifolia. Like other psoralens it causes photosensitization of the skin. It is administered either topically or orally in conjunction with UV-A (the least damaging form of ultraviolet light) for phototherapy treatment of vitiligo1 and hand eczema.2 After photoactivation it creates interstrand cross-links in DNA, which can cause programmed cell death unless repaired by cellular mechanisms. In research it can be conjugated to dyes for confocal microscopy and used to visualize sites of DNA damage.3 The compound is also being explored for development of antisense oligonucleotides that can be cross-linked specifically to a mutant mRNA sequence without affecting normal transcripts differing at even a single base pair.Trioxsalen was discontinued by the manufacturer in December 2002.