In the search for new anticancer drugs. 17. Linear and cyclic polyether analogues of N,N:N',N':N',N'-tri-1,2-ethanediylphosphoric triamide and N,N:N',N':N',N'-tri-1,2-ethanediylphosphorothioic triamide

Linear and cyclic polyether derivatives of N,N:N',N':N',N'-tri-1, 2-ethanediylphosphoric triamide (TEPA) and N,N:N',N':N',N'-tri-1,2-ethanediylphosphorothioic triamide (thio-TEPA) are synthesized and evaluated for their antineoplastic activity against the murine lymphocytic leukemia P388. All compounds, except for 7d, were active ranging from 42% to 287% increase in life span (% ILS). All CD2F1 male mice treated with the most active compound (7a) at 90 mg/kg per day for 9 days were alive after 30 days, whereas all mice treated with the clinical drug thio-TEPA were dead. The % ILS for compound 7a on day 60 was 525. A correlation is presented between the structural features of compounds and their lipophilicities and antineoplastic activities.     

The degradation of N,N',N"-triethylenephosphoramide in aqueous solutions: a qualitative and kinetic study

The degradation of N,N',N"-triethylenephosphoramide (TEPA) in aqueous solutions has been investigated over a pH range of 3-14. Samples were analyzed using a gas chromatographic system with nitrogen/phosphorus selective detection. The degradation kinetics were studied as function of pH, sodium chloride concentration and temperature. The degradation of TEPA in buffers follows pseudo first order kinetics. The logk(obs)8 the methoxy derivative of TEPA was formed, as a consequence of the applied procedure.     

Methyl 2-(2-chloroethylaminocarbonyl)diazenecarboxylate SB-166 inhibits the growth of different tumour cell lines, including drug-resistant sublines.

Recently we synthesized new drugs, diazenecarboxamides (shortly diazenes), that were cytotoxic for several tumour cell lines. Because the solubility and biological activity of these drugs was relatively low, new compounds have been synthesized. In the present study we examined the cytotoxic effect of nine compounds: an imidazolidin-2-one (SB-282: methyl 5-benzoyl-3-(2-chloroethyl)-2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-ylcarbamate), two diazenecarboxamides (UP-140: N-phenyl-2-(2-quinolinyl)diazenecarboxamide; JK-1090: N-(4-iodophenyl)-2-(2-pyridinyl)diazenecarboxamide), two aminocarbonyl substituted diazenecarboxylates (SB-178: methyl 2-[(cyclohexylamino)carbonyl]diazenecarboxylate; SB-166: methyl 2-[[(2-chloroethyl)amino]carbonyl]diazenecarboxylate) and four diazenedicarboxamides (SB-410: N(1)-(2-chloroethyl)-N(2)-(2-pyridinylmethyl)-1,2-diazenedicarboxamide; SB-472: N(1)-(2-chloroethyl)-N(2)-(4-isopropylphenyl)-1,2-diazenedicarboxamide; SB-503: N(1)-(4-sec-butylphenyl)-N(2)-(2-chloroethyl)-1,2-diazenedicarboxamide; SB-474: N(1)-(4-tert-butylphenyl)-N(2)-(2-chloroethyl)-1,2-diazenedicarboxamide). Using a modified colorimetric MTT assay, their cytotoxicity was determined on eight human cell lines: laryngeal carcinoma parental and two drug-resistant cell lines, glioblastoma parental and drug-resistant cell lines, cervical carcinoma parental and drug-resistant cell lines and breast adenocarcinoma cells. Results show that diazene SB-166 was very effective, reducing significantly the cell survival of all eight examined cell lines, including four drug-resistant cell lines. Compound SB-410 was cytotoxic for all examined cell lines, but mostly only in the highest concentration. Other compounds were not significantly cytotoxic to any of the treated cell lines. Our results, especially those obtained on drug-resistant cells, encourage further research on compound SB-166 as a potential anticancer drug.     

Evolution of a series of peptidoleukotriene antagonists: synthesis and structure/activity relationships of 1,3,5-substituted indoles and indazoles

1,3,5-Substituted indoles and indazoles have been studied as receptor antagonists of the peptidoleukotrienes. The best of these compounds generally had a methyl group at the N1 position, a [(cyclopentyloxy)carbonyl]amino or 2-cyclopentylacetamido or N'-cyclopentylureido group at the C-5 position, and an arylsulfonyl amide group as part of the acidic chain at the C-3 position of the ring. Such compounds had in vitro dissociation constants (KB) in the range 10(-9) - 10(-11) M on guinea pig trachea against LTE4 as agonist and inhibition constants (Ki) less than or equal to 10(-9) M on guinea pig parenchymal membranes against [3H]LTD4. A number of compounds were orally effective at doses less than or equal to 1 mg/kg in blocking LTD4-induced "dyspnea" in guinea pigs. Compound 45 [N-[4-[[5-[[(cyclopentyloxy)carbonyl]-amino]-1-methylindol-3- yl]methyl]-3-methoxybenzoyl]-2-methylbenzenesulfonamide, ICI 204,219; pKB = 9.67 +/- 0.13, Ki = 0.3 +/- 0.03 nM, po ED50 = 0.3 mg/kg] is currently under clinical investigation for asthma. In the indole series, certain alkylsulfonyl amides possessing a 3-cyanobenzyl substituent at the N-1 position (60, 61) were produced that had KB less than or equal to 10(-9) M on guinea pig trachea.     

Synthesis and in vitro pharmacology of arpromidine and related phenyl(pyridylalkyl)guanidines, a potential new class of positive inotropic drugs

Replacement of the cimetidine moiety in impromidine (1,N1-[3-(1H-imidazol-4-yl)propyl]-N2-[2-[[(5-methyl-1H-imidazol-4- yl)methyl]thio]ethyl]guanidine) by more lipophilic H2-nonspecific pheniramine-like structures resulted in potent H2 agonists with up to 160 times the activity of histamine in the isolated, spontaneously beating guinea pig right atrium. Additionally, the compounds proved to be moderate H1 antagonists. Highest H2-agonistic potency was found in compounds characterized by a three-membered carbon chain connecting the aromatic rings and the guanidine group. The activity in the atrium was increased 2-4-fold by halogen substituents in the meta or para position of the phenyl ring. Highest H1-antagonistic potency resides in the group of para-halogenated compounds, p-F representing the optimal substituent in both receptor models. The corresponding guanidine 52 (arpromidine, N1-[3-(4-fluorophenyl)-3-pyridin-2-ylpropyl]-N2-[3-(1H-imidazol-4- yl)propyl]guanidine) combines about 100 times the activity of histamine at the H2 receptor with H1-antagonistic potency in the range of pheniramine. Further increase in the activity on the atrium was achieved by disubstitution with halogen on the phenyl ring, such as 3,4-F2, 3,5-F2, and 3,4-Cl2 (63-65). The 2-pyridyl group in arpromidine was replaced by 3-pyridyl without significant change in H2 agonistic activity, whereas the 4-pyridyl and phenyl analogues were less active. The rank order of potency in the atrium was in good agreement with the positive inotropic effects found in isolated, perfused guinea pig hearts, where 63-65 were the most potent compounds as well.     

Rationally designed "dipeptoid" analogues of CCK. A Free-Wilson/Fujita-Ban analysis of some alpha-methyltryptophan derivatives as CCK-B antagonists.

A Free-Wilson/Fujita-Ban (FW/FB) analysis is reported on 36 "dipeptoid" antagonists of the CCK-B receptor. This series of compounds includes [R-(R*,R*)]-4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2- [[(tricyclo[3.3.1.1] dec-2-yloxy)carbonyl]amino]propyl]amino]-1-phenylethyl]amino]- 4-oxobutanoic acid (CI-988, 1, Figure 1), the first rationally designed non-peptide antagonist of a neuropeptide receptor. The analysis treats the compounds in three parts: the N-terminus, variants on the tryptophan moiety, and the C-terminus. A highly significant correlation was found (n = 36, r2 = 0.97, s = 0.22, F = 57, p = 2 x 10(-8)), suggesting that these three domains of these compounds contribute to binding affinity independently of each other, and are therefore additive in their effects on receptor affinity. The relative free-energies of binding of the individual substituents are calculated from the coefficients of the regression equation. The substitution of D-alpha-methyltryptophan for L-tryptophan increases the free-energy of binding by 3.5 kcal mol-1. This increase in binding energy is explained by a 300-fold difference in conformational entropy between the methylated and desmethyl analogues.     

头孢匹胺的合成

目的 研究头孢匹胺的合成工艺。 方法 (R)2-(6-甲基-4-羟基吡啶-3-羰基)-氨基]-2-(4-羟基苯基)乙酸乙酯(NPA-Et)经水解、成盐得到(R)2-(6-甲基-4-羟基吡啶-3-羰基)-氨基]-2-(4-羟基苯基)乙酸钠( NPA-Na)。NPA-Na与7-TMCA,即：(6R,7R)3-(1-甲基-1H-四唑-5-硫代甲基)-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸)缩合得头孢匹胺粗品,再成三乙胺盐,转酸,得到头孢匹胺成品。结果 第一步收率84.6%,第二步收率69.3%。结论     

Alkylation of DNA with aziridine produced during the hydrolysis of N,N',N'-triethylenethiophosphoramide.

A reaction pathway by which thiotepa (N,N',N'-triethylenethiophosphoramide) and tepa (N,N',N'-triethylenethiophosphoramide), its major metabolite in humans, alkylate and depurinate DNA involves hydrolysis to aziridine (ethylene imine), a highly reactive monofunctional alkylating agent. Hydrolytic cleavage of an N-P bond of thiotepa releases aziridine which reacts with DNA, resulting in depurination and formation of the stable N-7 adduct 7-(2-aminoethyl)guanine and an aminoethyl adduct of adenine. Chromatographically identical alkylated products were observed in the reaction of thiotepa and tepa with individual nucleosides. Adducts with deoxycytidine or thymidine were not detected. Aziridine was measured by HPLC after derivatization with 1,2-naphthoquinone 4-sulfate. On the basis of the identity of the DNA adducts and the rate of formation of aziridine by hydrolysis in vitro, thiotepa is concluded to be a lipophilic, stabilized form of aziridine which serves as a cell-penetrating carrier of aziridine.     

Synthesis and in vitro LTD4 antagonist activity of bicyclic and monocyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides

The dissociation constants (KB) at the LTD4 receptor on guinea pig trachea of a series of monocyclic and bicyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides have been measured. The KB was found to be remarkably tolerant of changes in the electronic constitution and lipophilicity of the bicyclic ring system (template). Thus, N-[4[[6-[[(cyclopentyloxy)carbonyl]amino]benzimidazol-1- yl]methyl]-3-methoxybenzoyl]benzenesulfonamide (11a) and N-[4-[[5-[[(cyclopentyloxy)carbonyl]amino]benzo[b]thien-3- yl]methyl]-3-methoxybenzoyl]benzene-sulfonamide (25a) had closely similar affinities (pKB, 9.20 and 9.31, respectively; LTE4 as agonist). It has been shown that the hetero-ring of the template need not be aromatic in order to achieve high affinity, since indoline 31 and 2,3-dihydrobenz-1,4-oxazines 37a-c had pKBs greater than 9. Further, it has been shown that an o-aminophenone (see 42 and Figure 3) can function as a template; the template in 42 [see iii] is bicyclic by virtue of the presence of an intramolecular hydrogen bond. In contrast, when the template is a phenyl ring (48), receptor affinity is markedly reduced. These findings support the notion that central bicyclic ring system in this family of peptidoleukotriene antagonists is a molecular feature which helps to preorganize the acylamino and acidic chains and thereby facilitate the molecular recognition event.     

Urinary excretion of thioTEPA and its metabolites in patients treated with high-dose cyclophosphamide, thioTEPA and carboplatin.

The urinary excretion of N,N',N"-triethylenethiophosphoramide (thioTEPA), and its metabolites N,N',N"-triethylenephosphoramide (TEPA), N,N'-diethylene,N"-2-chloroethylphosphoramide (monochloroTEPA) and thioTEPA--mercapturate was determined in patients receiving thioTEPA as part of a high-dose combination chemotherapy regimen with cyclophosphamide and carboplatin. The thioTEPA dose was 40 or 60 mg/m(2) in short infusions, twice daily, during 4 days. Urine samples were collected after each voiding on each day of drug administration until 24--48 h after the last thioTEPA infusion. ThioTEPA, TEPA and monochloroTEPA concentrations were determined with gas chromatography and thioTEPA--mercapturate with liquid chromatography--mass spectrometry with direct sample injection. ThioTEPA was present in urine 30 min after infusion and was still excreted 18 h after the last infusion. All metabolites were detected in urine 1 h after infusion. Patients with a creatinine clearance above 140 ml/minl showed higher excretion of TEPA than patients with a creatinine clearance below 140 ml/min (12.8 versus 4.9%, p=0.01). The excretion of monochloroTEPA relative to the excreted amount of TEPA increased at lower pH values of the urine. The excretion of thioTEPA--mercapturate relative to the dose was higher in patients treated with 60 mg/m(2). Excretion of thioTEPA and monochloroTEPA both accounted for only 0.5% of the dose, while TEPA and thioTEPA--mercapturate both accounted for 11.1%.     

Synthesis and in vivo evaluation of new contrast agents for cardiac MRI.

Analogues 2-6 of N(3),N(6)-bis(2'-myristoyloxyethyl)-1, 8-dioxotriethylenetetraamine-N,N,N',N'-tetraacetic acid (BME-DTTA) (1), which like 1 are also based on the DTTA structure but contain shorter fatty acyl chains, were synthesized to improve the water solubility of the corresponding gadolinium complexes. The gadolinium complexes of 1 and 3-5 have very low solubility in water. Thus liposomal preparations are necessary for their in vivo MRI application. These liposomal preparations retain high in vitro relaxivities (27.1, 21.57, 20.32, 23.1 s(-1) mM(-1), respectively) and induce sustained MRI signal intensity enhancements (67.2, 38.4, 52.1, 41.7 in arbitrary units, respectively). The gadolinium complex of 2 is quite soluble in water. Its lifetime in the blood stream, however, is short. The gadolinium complex of analogue 6, N-(2-butyryloxyethyl)-N'-(2-ethyloxyethyl)-N,N'-bis[N' ',N' '-bis(carboxymethyl)acetamido]-1,2-ethanediamine (ABE-DTTA), has demonstrated its potential as a water-soluble, cardiac-specific, MRI contrast agent. It is completely soluble in water at a 25 mM concentration, allowing the preparation of an injectable dose. The in vitro relaxivity of the complex is 16.24 s(-1) mM(-1). The agent shows a specific accumulation in the heart tissue reaching its maximum within 15 min after administration, inducing a sustained MRI signal intensity enhancement of 43.6%. This enhancement lasts for at least 3 h, thus indicating a reasonably long lifetime of this contrast agent in the myocardium without deleterious effects on heart function parameters.     

Retinobenzoic acids. 4. Conformation of aromatic amides with retinoidal activity. Importance of trans-amide structure for the activity

N-Methylation of two retinoidal amide compounds, 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benz oic acid (3, Am80) and 4-[[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)carbonyl]amino]benzoic acid (5, Am580), resulted in the disappearance of their potent differentiation-inducing activity on human promyelocytic leukemia cell line HL-60. Studies with 1H NMR and UV spectroscopy indicated that large conformational differences exist between the active secondary amides and the inactive N-methyl amides. From a comparison of the spectroscopic results of these amides with those of stilbene derivatives, the conformations of the active amides are expected to resemble that of (E)-stilbene, whereas the inactive amides resemble the Z isomer: 3 (Am80) and 5 (Am580) have a trans-amide bond and their whole structures are elongated, while the N-methylated compounds [4 (Am90) and 6 (Am590)] have a cis-amide bond, resulting in the folding of the two benzene rings. These structures in the crystals were related to those in solution by 13C NMR spectroscopic comparison between the two phases (solid and solution).     

Allosteric modifiers of hemoglobin. 1. Design, synthesis, testing, and structure-allosteric activity relationship of novel hemoglobin oxygen affinity decreasing agents

Three isomeric series of 2-(aryloxy)-2-methylpropionic acids were prepared and studied for their ability to decrease the oxygen affinity of human hemoglobin A. The isomeric aryloxy groups included 4-[[(aryloyl)amino]methyl]phenoxy, 4-(arylacetamido)phenoxy, and 4-[[(arylamino)carbonyl]methyl]phenoxy. A total of 20 compounds were synthesized and tested. Structure-activity relationships are presented. Several of the new compounds were found to be strong allosteric effectors of hemoglobin. The two most active compounds are 2-[4-[[(3,5-dichloroanilino)carbonyl]-methyl]phenoxy]- 2-methylpropionic acid and the corresponding 3,5-dimethyl derivative. The latter two compounds have been compared to other known potent allosteric effectors in the same assay and show greater activity. Both compounds also exhibit a right shift in the oxygen equilibrium curve when incubated with whole blood. The new compounds may be of interest in clinical or biological areas that require or would benefit from a reversal of depleted oxygen supply (i.e., ischemia, stroke, tumor radiotherapy, blood storage, blood substitutes, etc.). They are also structurally related to several marketed antilipidemic agents.     

Synthesis and biological characterization of new N-acyl-thiazolidine-4-carboxylic acid derivatives

2-Amino-1-[[(4-methoxycarbonylthiazolidin-3-yl)carbonyl]methyl]pyridinium chloride, 3-amino-1-[[(4-methoxycarbonylthiazolidin-3-yl)carbonyl]methyl]pyridinium chloride, 6-(3-aminopyridinium-1-yl)-5-oxo-5,7a-dihydro-1H-pyrrolo[1,2-c]thiazol-7-olate, and 6-(4-aminopyridinium-1-yl)-5-oxo-5,7a-dihydro-1H-pyrrolo[1,2-c]thiazol-7-olate were synthesized via the interaction of 3-chloroacetylthiazolidine-4-carboxylic acid methyl ester with 2-, 3-, and 4-aminopyridines. The synthesized compounds show significant influence on the learning and memorizing processes in experimental animals. An analysis of this activity in the tests involving cholinergic compounds showed that these N-acyl-thiazolidine-4-carboxylic acid derivatives are capable of influencing the central cholinergic system. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 10, pp. 9–12, October, 2007.     

2-氯-5-(5,6-二氢-2-甲基-1,4-氧硫杂环已二烯-3-甲酰胺基)苯甲酸异丙酯类似物的合成和生物活性(英文)

2-氯-5-(5,6-二氢-2-甲基-1,4-氧硫杂环已二烯-3-甲酰胺基)苯甲酸异丙酯(UC84)具有显著的抗病毒活性。合成了该化合物并以其为先导物模型制备了十一个结构未经报道的类似物，活性筛选试验表明该化合物有明显的抗乙肝病毒(HBV)和单纯疱疹病毒(HSV)活性。     

1,3,6-trisubstituted indoles as peptidoleukotriene antagonists: benefits of a second, polar, pyrrole substituent.

1,6-Substituted and 3,5-substituted indoles and indazoles containing acylamino and N-arylsulfonyl amide appendages are potent antagonists of the peptidoleukotrienes LTD4 and LTE4. A compound from the 3,5-substituted indole series, N-[4-[[5-[[(cyclopentyloxy)carbonyl]amino]-1-methylindol- 3-yl]methyl]-3-methoxybenzoyl]-2-methyl-benzenesulfonamide (ICI 204,219), is undergoing clinical evaluation for asthma. Two new elements of structural diversity were introduced to this series of antagonists. An investigation of pyrrole substituents in the 1,6-substituted indoles demonstrated that substitution at C-2 was detrimental to biological activity, but the incorporation of hydrophilic groups at C-3 was beneficial. The introduction of a propionamide moiety at C-3 enhanced activity by 1 order of magnitude; N-[4-[[6-(cyclopentylacetamido)-3-[2-(N- methylcarbamoyl)ethyl]indol-1-yl]methyl]-3-methoxy- benzoyl]benzenesulfonamide (15c) has a pKB of 10.7 at the LTD4 receptor on guinea pig trachea. Modifications of the acylamino portion of the disubstituted antagonists demonstrated that a transposition of the amide CO and NH atoms was viable. N-Cyclopentylmethyl amides in both the 1,6- and 3,5-disubstituted indole series were 1 order of magnitude less potent than the corresponding cyclopentylacetamides. In both series this potency loss could be regained by the incorporation of a propionamide substituent at either C-3 or N-1, respectively. For example, N-[4-[[6-[N-(cyclopentylmethyl)carbamoyl]-3-[2-(pyrrolidin-1 - methylbenzenesulfonamide (39c) has a pKB of 9.5.     

Synthesis and anti-measles virus activity of new isoquinolin-4-one derivatives

Despite intense efforts to increase vaccine coverage, measles virus (MV) still causes significant morbidity and mortality in the world sometimes as a results of severe, chronic and lethal diseases. In an effort to develop therapies to supplement immunization strategies a number of 1-oxo-2-[[(1E)-phenylmethylene]amino]-1,2-dihydroisoquinoline-4-carboxylic acid derivatives were synthesized and evaluated for anti-measles activity. The substituents on the aromatic ring were chosen in order to evaluate the influence of electron-withdrawing or electron-donating effects on the electronic density of the aromatic moiety. We also evaluated the introduction of a vinyl chain between the exocyclic nitrogen and phenyl moiety. The biological results allow to outline some preliminary considerations on structure-activity relationship.     

Antileukemic activity of substituted ureidothiazoles, ureidothiadiazoles, and related compounds.

A number of ureidothiazole and ureidothiadiazole derivatives related to ethyl 4-[[(2-thiazolylamino)carbonyl]-amino]benzoate were prepared and evaluated against the leukemia P-388 tumor system in mice. Preliminary structure-activity relationship study revealed that, among other considerations, active compounds of this series contain either an "isothioureido" [N-C(S-)=N-] or an "isothiosemicarbazono" [N-C(S-)=N-N=] structural unit.     

Synthesis of some new 6-methylimidazo[2,1-b]thiazole-5-carbohydrazide derivatives and their antimicrobial activities

In this study, 14 new compounds having 6-methyl-N2-(alkylidene/cycloalkylidene)imidazo[2,1-b]thiazole-5-carbohydrazide (3a-g), 3-[[(6-methylimidazo[2,1-b]thiazole-5-yl)carbonyl]amino]-4-thiazolidinone (4a-d) and 4-[[(6-methylimidazo[2,1-b]thiazole-5-yl)carbonyl]amino]-1-thia-4-azaspiro[4.4]nonan/[4.5]decan-3-one (4e-g) structures were synthesized. The structures of the compounds were elucidated by UV, IR, 1H-NMR, 13C-NMR, 1H-13C-COSY, mass spectra and elemental analysis. All compounds synthesized were tested for antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153, Candida albicans ATCC 10231 and Mycobacterium tuberculosis H37Rv. Only 4d and 4f demonstrated antimicrobial activity against S. epidermidis ATCC 12228 (MIC: 19.5 microg/ml and 39 microg/ml, respectively).     

Synthesis and siderophore activity of albomycin-like peptides derived from N5-acetyl-N5-hydroxy-L-ornithine.

N5-Acetyl-N5-hydroxy-L-ornithine (1), the key constituent of several microbial siderophores, has been synthesized in 23% yield overall from N-Cbz-L-glutamic acid 1-tert-butyl ester (6) derived from L-glutamic acid. Reduction of 6 to 7 and treatment with N-[(trichloroethoxy)carbonyl]-O-benzylhydroxylamine (8), and diethyl azodicarboxylate and triphenylphosphine followed by deprotection produced the protected N5-acetyl-N5-hydroxy-L-ornithine derivatives 11 and 12 in large quantities (10-20 g). Following alpha-amino and alpha-carboxyl deprotections of 11 and 12, EEDQ [2-ethoxy-N-(ethoxycarbonyl)-1,2-dihydroquinoline] mediated peptide coupling and final deprotection provided amino acid 1 and six albomycin-like peptides (20, 23, 25, 28, 35, and 36). The growth-promoting ability of each was evaluated with the siderophore biosynthesis mutant Shigella flexneri SA240 (SA 100 iucD:Tn5). These results indicate that substantial modification of the framework of peptide-based siderophores can be tolerated by microbial iron-transport systems.