Antimicrobial activity antitumor alkaloids

The syntheses of benzophenanthridine bases were also studied (132, 771-776). Much interest was shown in the synthesis of the alkaloids of this group, particularly after their antitumor activity in mouse leukemia L-1210 (LE) and P-388 (PS) as well as some selected antimicrobial activities had been established (776). On photocyclization, protopine, tetrahydroprotober-berine, and 13-methyltetrahydroprotoberberine yielded sanguinarine via anhydroprotopine (114) (680, 681, 777, 778) (Schemes 33 and 40). 

There is a group of antibiotics that possess the pyrrolo[l,4]benzodiazepine skeleton and show antimicrobial activity against Gram-positive bacteria, along with antiviral, antiphage, and antitumor activities. Anthramycin and tomaymycin are typical alkaloids in this group. 

The pharmacological activity of certain bisbenzylisoqui-noline alkaloids has been reviewed (Buck, 1987 Schiff, 1987). Many of these compounds have weak to moderate antimicrobial activity. Two types of bisisoquinoline alkaloids possess antitumor activity. These are bisbenzylisoqui-noline and aporphine-benzylisoquinoline alkaloids [e.g., tetrandrine (99) and thalicarpine (100), respectively]. Both have pronounced side effects (Cordell, 1978b). 

Recently, Kulp et al. observed a similar behavior in CZE analysis of isoquinoline alkaloids in extracts of Chelidoniwn majus L. [14]. These compounds exhibit distinct anti-inflammatory, antimicrobial, and antitumor activities, and the most effective alkaloid components of the plant are protopine, chehdonine, coptisine, sanguinarine, allocryptopine, and chelerythrine. Being strongly basic molecules with a heterocychc-bound nitrogen, these compounds show pKa values above 5 thus, in acidic... 

The majority of indolocarbazole alkaloids, isolated so far from nature, are derivatives of the indolo[2,3-fl]pyrrolo[3,4-c]carbazole ring system 292. They have been isolated from soil organisms, slime molds, and marine sources (3,7,8,252-255), and have shown a broad range of potent biological activities, such as antifungal, antimicrobial, antitumor, and antihypertensive activity (3,7,256-260,267-270). Their activity as potent inhibitors of protein kinase C (PKC) has received special attention, and was the focus of several investigations (8,257,258,271-280). The history of these natural products dates back about 30 years (Scheme 2.73). 

Manzamines comprise a new group of /3-carboline alkaloids having polycyclic ring systems, the provenance of which is problematical as there appears to be no obvious biogenetic path. Manzamine A (180) was isolated from an Okinawan sponge (Haliclona sp.) and shown to exhibit antitumor activity. Its structure and absolute configuration were determined by X-ray analysis (150). From an Okinawan sponge (Pellina sp.) keramamines A (180) and B (181) were isolated as antimicrobial substances (151), and keramamine A was found to be identical with manzamine A. 

Aristolochia clematitis has been used to treat snakebites and wound infections. One of the major alkaloids of this plant is aristolochic acid (46). The plant extract is not directly antimicrobial, but it produces an enhancement of phagocytosis of leucocytes and peritoneal microphages. Aristolochic acid is suspected to be carcinogenic (Pezzuto et al., 1988 Wagner and Proksch, 1985) and has been reported to have antitumor activity. The LD50 i.v. of aristolochic acid (46) in mouse is 38-70 mg/kg (Wink, 1993). 

This chapter describes research on natural aziridine alkaloids isolated from both terrestrial and marine species, as well as their lipophilic semisynthetic and/or synthetic analogues. Over 100 biologically active aziridine-containing compounds demonstrate confirmed pharmacological activity including antitumor, antimicrobial, and antibacterial effects. The structures, origin, and biological activities of aziridine alkaloids are reviewed. Consequently, this... 

This chapter reviews natural aziridine alkaloids, with high antitumor, antimicrobial, and antibacterial activities, and also highlights those semisynthetic derivatives and analogues which possess therapeutic promise. 

Aziridine alkaloids comprise a rare group of natural products. They are mainly isolated from either microorganisms or plants. They have also been detected in some marine species. Reported activities for purified alkaloids have shown strong antitumor, antibacterial, antimicrobial, and other activities. A wide spectrum of pharmacological activities is associated with this type of alkaloid which extends to selected synthetic derivatives. 

Carbazoles are pharmaceutically important heterocycles, and are attractive targets for organic chemists. Carbazole alkaloids are natural products exhibiting antitumor, antibacterial, antimicrobial, and antiinflammatory activities. Some carbazole derivatives display photoconducting and semiconducting properties. The nucleophylic approach can be used for the synthesis of the carbazole core. For example, intramolecular cyclization of 2-(6-substituted-3-(Z)-hexene-l,5-diyne)anilines 3.702 was accomplished for the synthesis of 5-carbazoles 3.703 in 65-85% yield (Scheme 3.76) [331]. 

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