The synthesis and evaluation of some 2'- and 7-amino acid derivatives of taxol (1) are reported. Reaction of taxol with N-protected amino acids gave 2'-N-protected amino acid esters of taxol. However, deprotection of the amino group and subsequent isolation of products were complex and only successful when formic acid was used to deprotect a t-BOC protecting group. Esterification of taxol using N,N-dialkylated amino acids gave 2'-amino acid esters of taxol, 2'-(N,N-dimethylglycyl)taxol (4) and 2'-[3-(N,N-diethylamino)propionyl]taxol as its methanesulfonic acid salt (5b), in good yield. The 7-derivatives, 7-(N,N-dimethylglycyl)taxol (9) and 7-L-alanyltaxol (12), were prepared by two alternate methods. In the first approach, the 2'-hydroxyl group was protected using the [(2,2,2-trichloro-ethyl)oxy]carbonyl, or troc, protecting group followed by the esterification of the 7-hydroxyl and subsequent deprotection of the amino and troc groups. In the second approach, taxol was allowed to react with more than 2 molar equiv of the N-protected amino acids or N,N-dialkylated amino acids to give 2',7-diamino acid esters of taxol. For the protected amino acids, the deprotection of the amino group followed by removal of the 2'-substituent gave the 7-amino acid esters of taxol. The methanesulfonic acid salts of both 2'- and 7-amino acid esters showed improved solubility ranging from 2 to greater than 10 mg/mL. The 7-derivatives were effective in promoting microtubule assembly in vitro while 2'-derivatives showed little in vitro activity. The derivatives 2'-(N,N-dimethylglycyl)taxol (4) and 2'-[3-(N,N-diethylamino)propionyl]taxol (5) inhibited proliferation of B16 melanoma cells to an extent similar to that of taxol, while the other derivatives were about 50% as cytotoxic. In a mammary tumor screen, 2'-[3-(N,N-diethylamino)propionyl]taxol showed the greatest antitumor activity compared to the other analogues. The lower activities of the 7-derivatives in inhibiting tumor growth and melanoma cell proliferation (although they were almost as active as taxol in inducing microtubule assembly in vitro) may be due to differences in drug uptake by the cells. The similar cytotoxic and antitumor activities of the 2'-analogues and taxol can be explained by their conversion to taxol or an active taxol metabolite. Therefore, the 2'-analogues appear to behave as prodrugs and have the potential to be developed as chemotherapeutic agents.

A number of chloro-substituted [(aminoalkyl)amino]anthraquinones were synthesized and evaluated for their antineoplastic and cytotoxic activity. Treatment of 5,8-dichloroquinizarin with substituted amines in pyridine resulted in the replacement of one halogen atom by the amino group to yield mainly 1-chloro-5,8-dihydroxy-4-(substituted amino)anthraquinones. On the other hand, reaction between the dichloroquinizarin and the amines in butanol gave predominantly 1,4-dichloro-5-hydroxy-8-(substituted amino)anthraquinones. Other compounds in this series were prepared by displacement of chloro, nitro, or tosyl functions of the appropriate anthraquinone derivatives with various amines by conventional methods. 1,4-Dichloro-5-hydroxy-8-[[2-[(2-hydroxyethyl)amino]ethyl]amino] anthraquinone (6b) possesses the highest inhibitory activity against P388 leukemia. Its inhibitory action against B16 melanoma and against the in vitro L1210 screen is also significant. Several other chloro- and hydroxy-substituted aminoanthraquinones (5a, 5b, and 6a) also showed noticeable activity against P388 in vivo and L1210 in vitro. Structure-activity-relationship examination indicated that the hydroxyl group may contribute to the binding of certain chloroaminoanthraquinones for their biological activity and that the [2-[(2-hydroxyethyl)amino]ethyl]amino side chain seems to be the preferred substituent over other amino side chains.

The synthesis of derivatives of 2,2,5,5‐tetramethylpyrrolidine nitroxide spin labels as pH sensitive probes is reported. The data on the pH sensitivity studies of these compounds indicate that the amino group increases the pH sensitivity of a nitroxide to a greater degree than a cyano, carboxyl or amido group.

Based on the observation of outstanding antineoplastic activity of a number of amino-substituted anthraquinones, thioxanthones, and N-(aminoethyl)-substituted naphthalimides, four types of amino-substituted p-benzoquinones were designed, synthesized, and their biological activity evaluated. Although none of these compounds exhibited inhibitory activity against P388 leukemia, 2,5-bis[[4-[(dimethylamino)methyl]phenyl]amino]-3,6-dibromo-1,4- benzoquinone and the corresponding dichloro compound demonstrated good inhibitory activity against the proliferating human colon adenocarcinoma in vitro. The dichloro compound was also found to be active against the leukemia L1210 screening in vitro. 2,5-Bis[[2-(dimethylamino)ethyl]amino]-1,4-benzoquinone possessed inhibitory activity against Neisseria catarrhali.

The current study is directed at identifying compounds that have biological activity in the less studied oil fraction of Curcuma longa (turmeric) to treat pancreatic cancer, which has no good treatment options. Fractional distillation and chromatographic separation of turmeric oil (TO) gave column fractions (CF) having biological activity against the PANC-1 pancreatic cancer cell line, with an EC 50 in the range of 23 to 33 g/mL. These fractions were analyzed by NMR and GCMS and found to contain the sesquiterpenes, ar-curcumene, 7-epi-zingiberene, -sesquiphellandrene, curlone, -turmerone, -turmerone and ar-turmerone. The ability of TO components to induce cell death was independent of caspase activity. Potency was higher at lower cell density and was reduced by increasing serum concentration, the latter indicating serum binding of active components.