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1.
Synthesis and bioactivity of 2,4-diacyl analogues of paclitaxel 总被引:1,自引:0,他引:1
Chordia MD Yuan H Jagtap PG Kadow JF Long BH Fairchild CR Johnston KA Kingston DG 《Bioorganic & medicinal chemistry》2001,9(1):171-178
The 2,4-diacyl paclitaxel analogues 8a-8r were prepared from paclitaxel by acylation of 4-deacetyl-2-debenzoylpaclitaxel 1,2-carbonate (3) followed either by hydrolysis of the carbonate and acylation or by direct treatment of the carbonate with an aryllithium. Some of the resulting derivatives showed significantly improved tubulin assembly activity and cytotoxicity as compared with paclitaxel; in some cases this improvement was especially significant for paclitaxel-resistant cell lines. 相似文献
2.
《Bioorganic & medicinal chemistry》2016,24(14):3116-3124
A derivative of the staurosporine aglycon (K252c), in which the lactam ring was replaced by a pyrazole moiety, was synthesized. The resulting indolopyrazolocarbazole (3) inhibited Pim isoforms 1–3 whereas it did not impair the activity of two known targets of K252c, protein kinase C isoforms α and γ. Compound 3 exhibited moderate cytotoxic activity toward human leukemia and colon carcinoma cell lines (K562 and HCT116), strongly suggesting that this new scaffold deserves further investigations for treatment of malignancies associated with Pim activity. 相似文献
3.
The reduction of castasterone with sodium in ethanol produced chiefly the known 6alpha-hydroxy stereoisomer, whereas reduction with sodium orohydride in methanol afforded mainly the novel 6beta-epimer. Both compounds showed variable bioactivity through four separate assays via the rice leaf lamina inclination bioassay. However, when treated with an appropriate statistical program to remove outliers, the averaged results clearly indicated that the two 6-hydroxy epimers possess comparable and significant bioactivity, which is, however, lower than that of castasterone or brassinolide. When applied together with 1000 ng of the auxin, indole-3-acetic acid (IAA), the activity of both the 6alpha and 6beta hydroxy epimers was enhanced by ca. one order of magnitude across a wide range of doses. 相似文献
4.
Synthesis and evaluation of vancomycin and vancomycin aglycon analogues that bear modifications in the residue 3 asparagine 总被引:1,自引:0,他引:1
The synthesis and biological evaluation of a set of residue 3 analogues of vancomycin and its aglycon are described. These investigations follow from the promising biological activity of a protected and synthetically modified vancomycin aglycon analogue in which the asparagine side chain was modified to possess a nitrile, rather than a carboxamide. Although this modification typically was detrimental to antimicrobial activity, hydrophobic vancomycin aglycon analogues that lack a lipid anchor as well as the disaccharide are detailed that exhibit unusual potency against VanB, but not VanA, resistant bacteria. 相似文献
5.
Salmon melanin concentrating hormone (MCH) is a cyclic heptadecapeptide. MCH stimulates perinuclear aggregation of melanosomes within integumental melanocytes of teleost fishes resulting in skin blanching. MCH contains a disulfide bridge forming a 10-residue ring [sequence: see text]. It has been proposed that the ring is necessary for maintenance of potency. In order to test this proposal, we have synthesized two pseudo-isosteric analogues of MCH that cannot cyclize. They differed only in the polarity of the side chain group of positions 5 and 14. Serine was substituted for Cys5 and Cys14 in one peptide and L alpha-aminobutyrate (Abu) was the substitution at the two positions in the other peptide. Using a fish skin bioassay we determined that these analogues exhibit less than 1/10,000th the potency of the native hormone. These results suggest that the disulfide bridge is necessary to maintain the correct conformational and topographical features of the hormone for receptor binding and transmembrane signal transduction. 相似文献
6.
Seven aglycon analogs of globotriosylceramide were synthesized by glycosylation of suitable functionalized alcohols with peracetylated globotriose trichloroacetimidate, followed by further transformations of the aglycon and removal of the protecting groups. 相似文献
7.
In this paper, we report the synthesis and bioactivity of four synthetic analogues of 28-homobrassinosteroids, in order to evaluate the influence in bioactivity when the C-6 keto group is replaced by different functional groups. The synthetic analogues are 6-deoxo-28-homocastasterone [(22R,23R)-stigmasta-2alpha,3alpha,22,23-tetraol], 6alpha-hydroxy-28-homocastasterone [(22R,23R)-stigmasta-2alpha,3alpha,6alpha,22,23-pentaol], 6beta-hydroxy-28-homocastasterone [(22R,23R)-stigmasta-2alpha,3alpha,6beta,22,23-pentaol], and [(22R,23R)-6alpha-fluorostigmasta-2alpha,3alpha,22,23-tetraol]. Results indicate that replacement of the 6-keto moiety by an beta or alpha hydroxyl group led to a decrease in activity, whereas the 6-deoxo analogue showed a very low activity, confirming the importance of an electronegative moiety at C-6 to observe hormonal potency. The 6alpha-fluorinated analogue elicited a low activity, similar to that of the 6-deoxo analogue. 相似文献
8.
Andrea Dalla Bona Fernando Formaggio Cristina Peggion Bernard Kaptein Quirinus B Broxterman Stefania Galdiero Massimiliano Galdiero Mariateresa Vitiello Ettore Benedetti Claudio Toniolo 《Journal of peptide science》2006,12(12):748-757
We synthesized by solution-phase methods three analogues, [L-Leu(6)-OMe], [L-(alphaMe)Leu(3), L-Leu(6)-OMe], and [L-(alphaMe)Val(4), L-Leu(6)-OMe] of halovir A. The [L-Leu(6)-OMe] analogue is known to be biologically equipotent to its naturally occurring, antiviral, lipopentapeptide amide parent compound. The preferred conformations of the L-(alphaMe)Leu- and L-(alphaMe)Val-containing analogues, with a potentially reinforced helicity, were compared with those of [L-Leu(6)-OMe] halovir A and the natural peptide itself by use of a combination of FT-IR absorption and NMR techniques. Measurements of the antiviral activities against herpes simplex virus type-1 (HSV-1) of halovir A and its three analogues were also carried out. Interestingly, the [L-(alphaMe)Val(4), L-Leu(6)-OMe] analogue exhibits the most significant activity in reducing HSV-1 infectivity, notably higher than that of halovir A itself. 相似文献
9.
Srivastava V Darokar MP Fatima A Kumar JK Chowdhury C Saxena HO Dwivedi GR Shrivastava K Gupta V Chattopadhyay SK Luqman S Gupta MM Negi AS Khanuja SP 《Bioorganic & medicinal chemistry》2007,15(1):518-525
Several diverse analogues of Oenostacin, a naturally occurring potent antibacterial phenolic acid derivative, have been synthesized. A small library with more than forty analogues having different aromatic rings and varied side chains has been achieved through solution phase synthesis. Some of these analogues, that is, 22, 23 and 42, possessed potent antibacterial activities against Staphylococcus epidermidis and Staphylococcus aureus having EC(50) ranging from 0.49 to 0.67 microM as compared to Oenostacin (EC(50)=0.12 microM). 相似文献
10.
Young Lok Choi Joa Kyum Kim Sang-Un Choi Yong-Ki Min Myung-Ae Bae Bum Tae Kim Jung-Nyoung Heo 《Bioorganic & medicinal chemistry letters》2009,19(11):3036-3040
A series of natural aristolactams and their analogues have been prepared and evaluated for antitumor activity against human cancer cells, including multi-drug resistant cell lines. Naturally occurring aristolactams, such as aristolactam BII (cepharanone B), aristolactam BIII, aristolactam FI (piperolactam A), N-methyl piperolactam A, and sauristolactam showed moderate antitumor activities in selected cell lines. However, several synthetic aristolactam derivatives exhibited potent antitumor activities against a broad array of cancer cell lines with GI50 values in the submicromolar range. 相似文献
11.
Cesnek M Holý A Masojídková M Kmonícková E Zídek Z 《Bioorganic & medicinal chemistry》2008,16(2):965-980
A series of novel 9-, 7- and 3-substituted 2- or 6-guanidinopurines as analogues of potent antiviral and immunobiologically active compound enantiomers of PMPDAP was synthesized and evaluated for their biological activity. Compounds containing the combination of guanidino and amino group at the purine moiety enhanced the interferon-gamma-triggered NO production in murine macrophages and stimulated the secretion of cytokines and chemokines in both murine macrophages and human peripheral blood mononuclear cells. The most active compounds are 27 and 54. None of the compounds tested exhibited any significant cytostatic effect or antiviral effect. 相似文献
12.
Zha-Jun Zhan Hong-Ling Bian Jian-Wei Wang Wei-Guang Shan 《Bioorganic & medicinal chemistry letters》2010,20(5):1532-1534
A series of physostigmine analogues were prepared and evaluated for cholinesterase inhibition activities, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of them showed potent inhibition activities against AChE, in which compound 17 especially exhibited significantly higher selectivity over BChE than phenserine, a compound currently on clinical trial. Discussion about the relationships between structure and activity of these derivatives was also presented. 相似文献
13.
A small library of N-For and N-Boc tetrapeptidic analogues of the chemotactic tripeptide For-Met-Leu-Phe-OMe (fMLF-OMe), obtained by incorporating three
different spacer aminoacids (Gly, βAla and Pro) between the native residues of Met and Leu (N-For- and N-Boc-Met-Xaa-Leu-Phe-OMe; Xaa2 series) and Leu and Phe (N-For- and N-Boc-Met-Leu-Xaa-Phe-OMe; Xaa3 series), have been synthesized and examined for their biological activity as agonists and antagonists. Chemotaxis, lysozyme
release and superoxide anion production have been measured. All the N-For analogues maintain good to moderate chemotactic activity with the βAla3
15 model reaching the maximum value. All the N-Boc tetrapeptides are efficient chemotactic antagonists. Conversely, with the exception of the moderate antagonistic activity
exhibited by the N-Boc Xaa2 models against lysozyme release, all the other N-Boc analogues do not show significant activity against both superoxide anion and lysozyme release. 相似文献
14.
Synthesis of selenium-containing amino acid analogues is described. These compounds were prepared in a concise and short synthetic
route in good yields by nucleophilic substitution reaction of pyridineselenol and quinolineselenol derivatives with N-phthaloylglycyl chloride followed by hydrazinolysis. The newly synthesized compounds were screened against different strains
of bacteria and fungi. 相似文献
15.
Terracciano S Bruno I Bifulco G Avallone E Smith CD Gomez-Paloma L Riccio R 《Bioorganic & medicinal chemistry》2005,13(17):5225-5239
Recently, we described the synthesis and the biological evaluation of three modified analogues of jaspamide (1), a natural cyclodepsipeptide possessing a potent antitumor activity as a consequence of its ability to interfere with actin cytoskeleton. To obtain additional information on the potential pharmacophoric core of the target molecule, which is of fundamental importance to discover new and more effective anticancer products, we decided to explore the biological effects of further structural modifications carried out on the parent molecule. The synthesis and the chemical characterization of six jaspamide analogues (2-7) are reported and their conformational and biological properties are described. 相似文献
16.
《Bioorganic & medicinal chemistry》2019,27(11):2209-2219
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease and remains incurable. Currently, neuronal injury and synapse loss have been considered to be main features in the pathophysiology of AD. Thus, modulation of neuronal survival and neurite outgrowth may represent an efficient strategy for the treatment of AD. Based on the isolates from the traditional medicine Andrographis paniculata, a series of andrographolide analogues were prepared and evaluated for the neuroprotection and neurotrophic activity. Two compounds (3 and 12) could effectively inhibit LPS-induced NO production and iNOS expression as well as proinflammatory cytokines TNF-α and IL-6. Moreover, pretreatment with 3 and 12 could protect neurons against microglia-mediated neurotoxicity. Further, H2O2− and 6-OHDA induced neurotoxicity in PC12 cells were also attenuated by the novel 12. Our next study indicated that compounds 1, 4 and 10 promoted NGF-induced neurite outgrowth in PC12 cells, with 10 the most potent. To clarify the underlying mechanisms of active compounds (3, 10 and 12), system pharmacology was employed. The results revealed that muscarinic acetylcholine receptors (mAChRs) may be the main targets of 12 against AD, while thyroid hormone signaling pathway was involved in the mechanisms of 10. These study point to the therapeutic potential of andrographolide analogues against AD. 相似文献
17.
Takahashi M Dodo K Sugimoto Y Aoyagi Y Yamada Y Hashimoto Y Shirai R 《Bioorganic & medicinal chemistry letters》2000,10(22):2571-2574
The novel analogues of natural cdc25A inhibitor dysidiolide were synthesized. To investigate the structure-activity relationship, the inhibitory activity to enzyme and cell cycle was examined. 相似文献
18.
Iminoalditol analogues of galactofuranosides were synthesized from 1-C-(2′-oxo-propyl)-1,4-dideoxy-1,4-imino-d-galactosides and different amines by reductive amination, followed by removal of protecting groups. The activity of these compounds against galactosidases and other glycosidases was investigated. The best inhibitor against β-galactosidase (bovine liver) is a diastereomeric mixture of an iminoalditol (10h), which contains a hydrophobic hexadecyl aglycon (R = C16H33), whereas no significant inhibitory activity was observed with compounds having a hydrophilic aglycon. Surprisingly, activation of α-galactosidase (coffee bean) by 10h was also observed. Because these results were obtained from a mixture of iminoalditols, the inhibition and activation of glycosidases could result from different diastereomers. 相似文献
19.
20.
M Shinada F Narumi Y Osada K Matsumoto T Yoshida K Higuchi T Kawasaki H Tanaka M Satoh 《Bioorganic & medicinal chemistry》2012,20(16):4901-4914
Phenserine is a potentially attractive drug for Alzheimer's disease. In order to further expand SAR study for inhibitions of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), the methyl group at the 3a-position of phenserine was replaced with an alkyl or alkenyl group, and its phenylcarbamoyl moiety was substituted at the o- or p-position. The synthetic methodology for these phenserine analogues includes the efficient cascade reactions for introduction of the 3a-substituent and assembly of the quaternary carbon center followed by reductive cyclization to the key pyrroloindoline structure. The bulkiness of the substituent at 3a-position of phenserine derivatives tends to reduce the inhibitory effect on AChE activity in the following order: methyl>ethyl>vinyl>propyl≈allyl>reverse-prenyl groups. Among the series synthesized, the 3a-ethyl derivative demonstrated the highest AChE selectivity. In construct, the 3a-reverse-prenyl derivative indicated modest BuChE selectivity. 相似文献