Synthesis and antitumor activity of CBI-bearing ester and carbamate prodrugs of CC-1065 analogue

Prodrugs of a CBI-bearing CC-1065 analogue were synthesized. Antitumor activity of the compounds was evaluated against tumor cells in vitro and in mouse tumor models. Compounds 1 and 7, bearing methylpiperazine and DHA moieties, respectively, showed significant antitumor activity in both the L1210 leukemia and Lewis lung carcinoma mouse tumor models. For the carbamate prodrugs 1-4 and 6, there is a good correlation between the drug's potency both in vitro and in animal tumor models; however, there is no correlation between the prodrug's antitumor activity and the type of bonds linking the free drug. There are no significant differences between the antitumor activities of those that can or cannot be protonated at physiological pH. Compounds 6 and 7, each bearing a DHA moiety, did not show significantly improved antitumor activity compared to other prodrugs bearing DHA moieties, suggesting that DHA may not be used universally to significantly improve a drug's antitumor efficacy.     

Synthesis and antitumor activity of cyclodepsipeptide zygosporamide and its analogues

The synthesis and structure–activity relationships of zygosporamide, a known potent and selective cytotoxic natural product against SF-268 and RXF 393 cell lines, are described. The potencies of the synthetic zygosporamide are similar to those reported for the natural product toward all cancer cell lines examined with the exception of SF-268, the underlying cause of which remains to be elucidated.     

Synthesis and antitumor activity of fluorocyclopentenyl-pyrimidines

Synthesis of fluorocyclopentenyl pyrimidine nucleosides 6-9 was enantiopurely accomplished employing oxidative rearrangement, RCM reaction and electrophilic fluorination starting from d-ribose. Cytosine analog 8 was found to exhibit significant anticancer activity in various human tumor cell lines.     

Synthesis and cytotoxicities of icogenin analogues with disaccharide residues

For further structure–activity relationships (SAR) research of furostan saponin, two icogenin analogues: (25R)-22-O-methyl-furost-5-en-3β,26-diol-3-O-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranoside 1 and (25R)-22-O-methyl-furost-5-en-3β,26-diol-3-O-α-l-rhamnopyranosyl-(1 → 2)-α-d-glucopyranoside 2, with valuable disaccharide moieties, were synthesized from diosgenin through eight steps. Both of the analogues behaved the similar cytotoxic activities with icogenin, towards nine types of human tumor cells herein.     

Synthesis and antimicrobial activity of squalamine analogue

Synthesis and antimicrobial activity of squalamine analogue 2 are reported. The synthesis of 2 was accomplished from bisnoralcohol 3. The spermidine moiety was introduced via reductive amination of an appropriately functionalized 3beta-aminosterol with spermidinyl aldehyde 17 utilizing sodium triacetoxyborohydride as the reducing agent. Compound 2 shows weaker antimicrobial activity than squalamine.     

Synthesis and antitumor activity of 3'-C-methyl-daunorubicin

Reaction of 1,5-anhydro-4-O-benzoyl-2,3,6-trideoxy-3-C-methyl-3-trifluoro-acetami no-L-lyxo-hex-1-enitol with daunomycinone in the presence of anhydrous toluene-p-sulfonic acid in benzene, followed by removal of the N- and O-protecting groups under mild conditions, gave 3'-C-methyldaunorubicin. The antitumor activity of the new anthracycline glycoside has been evaluated.     

Synthesis and antitumor activity of s-tetrazine derivatives

Fifty-five compounds of s-tetrazine derivative including hexahydro-, 1,6-dihydro, 1,4-dihydro-, 1,2-dihydro- and aromatic s-tetrazine were prepared. Their antitumor activities were evaluated in vitro by MTT method for P-388 cell and SRB method for A-549 cell. The results show that there are 9 compounds which in 10(-6) microM have more than 50% inhibition rate to A-549 cancer cell growth, and 7 compounds in 10(-6) microM have more than 50% inhibition rate to P-388 cancer cell growth. The IC(50) of compound 3q for P-388, Bel-7402, MCF-7 and A-549 are 0.6 microM, 0.6 microM, 0.5 microM and 0.7 microM, respectively. So s-tetrazine derivative is a kind of compound which possesses potential antitumor activities and is worth to research further.     

白藜芦醇及其水溶性衍生物的合成

目的:合成白藜芦醇及其水溶性衍生物。方法:以3,5-二甲氧基苯甲醛和4-甲氧基碘苯为原料,经Wittig反应,Heck偶联,脱甲基反应,连接侧链等合成白藜芦醇及其衍生物,并使用紫外法测定其在水中的溶解度大小。结果:目标化合物经核磁共振氢谱,质谱等确证为白藜芦醇及其水溶性衍生物,且水溶性提高3倍。结论:该方法的反应路线步骤短,操作简便,对反式产物选择性高。     

Synthesis and antifungal activity of a ferrocene-fluconazole analogue

A novel ferrocene fluconazole analogue was synthesized and its antifungal properties investigated against yeast strains of medical importance, including those intrinsically resistant to fluconazole. In vitro tests revealed a slight increase in fungal growth and a reversal of the effect of fluconazole at minimal inhibitory concentrations.     

Synthesis and antitumor activity of simplified ecteinascidin-saframycin analogs

Two series of simplified analogs of the ecteinascidin-saframycin type alkaloids were prepared from l-DOPA. Their in vitro antitumor activity was tested against three human cancer cell lines (HCT-8 colon carcinoma, Bel-7402 liver carcinoma, and BGC-823 gastric carcinoma). Among these compounds, the ester analogs have stronger activities than those of amide analogs in general. Among them, 1-naphthalene carboxylate ester analog 31 has the strongest activity against BGC-823 cells.     

Synthesis and antitumor activity of goniofufurone analogues.

Synthesis and antitumor activity of goniofufurone analogues 15, 16, 17, 33, and 46 is reported. Key step in the synthesis is Pd (II) mediated oxidative cyclisation of vinyl-(hydroxy) furans 18, 19 to the corresponding lactols 32, 43. Cytotoxicities of 15, 16, 17, 33, and 46 tested against six human cancer cell lines are reported. Change of stereochemistry at C-5, C-6 and C-7 position of goniofufurone (1) did not enhance the cytotoxicities significantly.     

Synthesis and antitumor activity of 10-arylcamptothecin derivatives

A series of 10-arylcamptothecin derivatives was designed and synthesized. The key step of the synthesis was achieved by employing Suzuki cross-coupling chemistry. All of the new derivatives were tested for cytotoxicity against three human tumor cell lines, BEL-7402, A549, and HL-60; most of the derivatives exhibited potent cytotoxicity. The stability study showed that compound 30 was more stable than its lead compound 10-hydroxycamptothecin under the physiological condition. Mechanistic study demonstrated that compound 30 and its hydrochloride 31 had a pharmacological profile similar with camptothecin.     

Synthesis and antitumor activity of peptide-paclitaxel conjugates.

Paclitaxel (Pac) is the most important anticancer drug used mainly in treatment of breast, lung, and ovarian cancer and is being investigated for use as a single agent for treatment of lung cancer, advanced head and neck cancers, and adenocarcinomas of the upper gastrointestinal tract. In this work, we present the synthesis of five 2'-paclitaxel-substituted analogs in which paclitaxel was covalently bound to peptides or as multiple copies to synthetic carriers. Ac-Cys(CH(2)CO-2'-Pac)-Arg-Gly-Asp-Arg-NH(2), Folyl-Cys(CH(2)CO-2'-Pac)-Arg-Gly-Asp-Ser-NH(2), Ac-[Lys-Aib-Cys(CH(2)CO-2'-Pac)](2)-NH(2), Ac-[Lys-Aib-Cys(CH(2)CO-2'-Pac)](3)-NH(2) and Ac-[Lys-Aib-Cys(CH(2)CO-2'-Pac)](4)-NH(2) were synthesized using 2'-halogeno-acetylated paclitaxel derivatives. Paclitaxel conjugates showed greater solubility in water than paclitaxel and inhibited the proliferation of human breast, prostate, and cervical cancer cell lines. Although all synthesized compounds had an antiproliferative activity, the Ac-[Lys-Aib-Cys(CH(2)CO-2'-Pac)](4)-NH(2) derivative showed improved biological activity in comparison with paclitaxel in cervical and prostate human cancer cells.     

Synthesis and antitumor activity of novel paclitaxel-chlorambucil hybrids

The syntheses and antitumor activity of three paclitaxel-chlorambucil hybrids are presented. Hybrid 3 showed significant in vivo efficacy.     

Synthesis and antitumor activity of 4-hydroxycoumarin derivatives

A series of 4-hydroxycoumarin derivatives was prepared and evaluated for antitumor activity. The key fragments were 2a-c, 5c, 12b, 13b, 17, and 18 which were prepared via dianion ring cyclization, Friedel-Crafts acylation, and Reformatsky reaction. Compound 20b showed the most potent antitumor activity among the total 12 derivatives and compounds 19a and 19b exhibited efficacy comparable to etoposide in vitro antitumor activity.     

Synthesis and antitumor activity of new retinobenzoic acids

New retinobenzoic acid derivatives have been synthesized starting from 1,2,3,4-tetrahydro-1,1,2,4,4,6-hexamethylnaphthalene and 1,1,2,3,3-pentamethylindane. Four of the synthetic compounds displayed potent cytotoxic activities in vitro against human breast cancer and leukemic cell lines. Thus, these molecules can be further evaluated for the treatment of human leukemia and breast cancer.     

Synthesis and biological activity of brassinolide analogues, 26,27-bisnorbrassinolide and its 6-oxo analogue

Two hitherto unknown brassinolide analogues, (22R,23R)-2α,3α,22,23-tetrahydroxy-B-homo-7-oxa-24-nor-5α-cholestan-6-one (9b) and (22R,23R)-2α,3α,22,23-tetrahydroxy-24-nor-5α-cholestan-6-one (8a), were stereoselectively synthesized. In both the Raphanus and rice-lamina inclination tests, 9b exhibited almost the same activity as brassinolide (1) and 8a also showed ca 10–50% of the activity of 1.     

Synthesis of cholestane glycosides bearing OSW-1 disaccharide or its 1→4-linked analogue and their antitumor activities

For further structure–activity relationship (SAR) research of OSW saponins, a cholestane glycoside, namely 3β, 16β, 26-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-β-d-xylopyranosyl)-(1→3)-2-O-acetyl-α-l-arabinopyranoside (1) together with two 1→4-linked disaccharide analogues (2 and 3) were synthesized. Their cytotoxic activities were evaluated by the standard MTT assay. Compound 1 showed potent cytotoxicity against five types of human tumor cells, with IC₅₀ ranging between 1.3 and 73 nM.     

Synthesis and antitumor activity of feruloyl and caffeoyl derivatives

We developed two efficient protocols for the synthesis of feruloyl and caffeoyl derivatives from commercial vanillin and veratraldehyde. Pharmacological activities were assessed against a panel of human cancer cell lines in vitro. Most synthesized compounds demonstrated attractive cytotoxicity. Several new compounds demonstrated significant antiproliferative and cytotoxic activities against HeLa and Bewo tumor cell lines. In particular, 5-nitro caffeic adamantyl ester showed broad spectrum of tumor inhibition in 10 cell lines, and reduced tumor weight by 36.7% in vivo when administered at a dose of 40 mg kg⁻¹.     

Synthesis and radical-scavenging activity of a dimethyl catechin analogue

Catechin analogue 1 with methyl substituents ortho to the catechol hydroxyl groups was synthesized to improve the antioxidant ability of (+)-catechin. The synthetic scheme involved a solid acid catalyzed Friedel–Crafts coupling of a cinnamyl alcohol derivative to 3,5-dibenzyloxyphenol followed by hydroxylation and then cyclization through an intermediate orthoester. The antioxidative radical scavenging activity of 1 against galvinoxyl radical, an oxyl radical, was found to be 28-fold more potent than (+)-catechin.