scholarly journals Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

2012 ◽  
Vol 8 ◽  
pp. 861-869 ◽  
Author(s):  
Tobias Knobloch ◽  
Gerald Dräger ◽  
Wera Collisi ◽  
Florenz Sasse ◽  
Andreas Kirschning
Keyword(s):  
Antiproliferative Activity ◽  
Side Chain ◽  
Actinosynnema Pretiosum

We describe the unprecedented formation of six ansamitocin derivatives that are deoxygenated at C-7 of the ansamitocin core, obtained during fermentation experiments by employing a variety of Actinosynnema pretiosum mutants and mutasynthetic approaches. We suggest that the formation of these derivatives is based on elimination at C-7/C-8 followed by reduction(s) of the intermediate enone. In bioactivity tests, only ansamitocin derivatives bearing an ester side chain at C-3 showed strong antiproliferative activity.

scholarly journals Preparation of new alkyne-modified ansamitocins by mutasynthesis

2014 ◽  
Vol 10 ◽  
pp. 535-543 ◽  
Author(s):  
Kirsten Harmrolfs ◽  
Lena Mancuso ◽  
Binia Drung ◽  
Florenz Sasse ◽  
Andreas Kirschning
Keyword(s):  
Antiproliferative Activity ◽  
Tumor Targeting ◽  
Side Chain ◽  
Aminobenzoic Acids ◽  
Actinosynnema Pretiosum ◽  
The Way

The preparation of alkyne-modified ansamitocins by mutasynthetic supplementation of Actinosynnema pretiosum mutants with alkyne-substituted aminobenzoic acids is described. This modification paved the way to introduce a thiol linker by Huisgen-type cycloaddition which can principally be utilized to create tumor targeting conjugates. In bioactivity tests, only those new ansamitocin derivatives showed strong antiproliferative activity that bear an ester side chain at C-3.

Synthesis of Some Steroidal Derivatives with Side Chain of 20- and 22- Hydrazone Aromatic Heterocycles and their Antiproliferative Activity

2017 ◽  
Vol 13 (4) ◽  
pp. 375-383 ◽  
Author(s):  
Chunfang Gan ◽  
Liang Liu ◽  
Jianguo Cui ◽  
Zhiping Liu ◽  
Haixin Shi ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Side Chain ◽  
Aromatic Heterocycles ◽  
Steroidal Derivatives

scholarly journals Synthesis, Microtubule-Binding Affinity, and Antiproliferative Activity of New Epothilone Analogs and of an EGFR-Targeted Epothilone-Peptide Conjugate

2019 ◽  
Vol 20 (5) ◽  
pp. 1113 ◽  
Author(s):  
Fabienne Gaugaz ◽  
Andrea Chicca ◽  
Mariano Redondo-Horcajo ◽  
Isabel Barasoain ◽  
J. Díaz ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Antiproliferative Activity ◽  
Growth Factor Receptor ◽  
Side Chain ◽  
Cancer Cell Growth ◽  
Microtubule Binding ◽  
Egfr Expression ◽  
Epidermal Growth ◽  
Viable Approach

A new simplified, epoxide-free epothilone analog was prepared incorporating an N-(2-hydroxyethyl)-benzimidazole side chain, which binds to microtubules with high affinity and inhibits cancer cell growth in vitro with nM potency. Building on this scaffold, a disulfide-linked conjugate with the purported EGFR-binding (EGFR, epidermal growth factor receptor) peptide GE11 was then prepared. The conjugate retained significant microtubule-binding affinity, in spite of the size of the peptide attached to the benzimidazole side chain. The antiproliferative activity of the conjugate was significantly lower than for the parent scaffold and, surprisingly, was independent of the EGFR expression status of cells. Our data indicate that the disulfide-based conjugation with the GE11 peptide is not a viable approach for effective tumor-targeting of highly potent epothilones and probably not for other cytotoxics.

Synthesis and antiproliferative activity of side-chain unsaturated and homologated analogs of 1,25-dihydroxyvitamin D2

Steroids ◽  
2002 ◽  
Vol 67 (9) ◽  
pp. 789-798 ◽  
Author(s):  
Michał Chodyński ◽  
Joanna Wietrzyk ◽  
Ewa Marcinkowska ◽  
Adam Opolski ◽  
Wiesław Szelejewski ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Side Chain

scholarly journals Bicyclic Basic Merbarone Analogues as Antiproliferative Agents

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 557
Author(s):  
Andrea Spallarossa ◽  
Matteo Lusardi ◽  
Chiara Caneva ◽  
Aldo Profumo ◽  
Camillo Rosano ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Side Chain ◽  
The Novel ◽  
Bioactive Conformation ◽  
Pyrimidine Derivatives ◽  
Topoisomerase Iiα ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Step Procedure ◽  
Pyrimidine Moiety

Pyrimido-pyrimidine derivatives have been developed as rigid merbarone analogues. In a previous study, these compounds showed potent antiproliferative activity and efficiently inhibited topoisomerase IIα. To further extend the structure–activity relationships on pyrimido-pyrimidines, a novel series of analogues was synthesized by a two-step procedure. Analogues 3–6 bear small alky groups at positions 1 and 3 of the pyrimido-pyrimidine scaffold whereas at position 6a (4-chloro)phenyl substituent was inserted. The basic side chains introduced at position 7 were selected on the basis of the previously developed structure–activity relationships. The antiproliferative activity of the novel compounds proved to be affected by both the nature of the basic side chain and the substituents on the pyrimido-pyrimidine moiety. Derivatives 5d and 5e were identified as the most promising molecules still showing reduced antiproliferative activity in comparison with the previously prepared pyrimido-pyrimidine analogues. In topoisomerase IIα-5d docking complex, the ligand would poorly interact with the enzyme and assume a different orientation in comparison with 1d bioactive conformation.

Molecular structures and antiproliferative activity of side-chain saturated and homologated analogs of 2-chloro-3-(n-alkylamino)-1,4-napthoquinone

2013 ◽  
Vol 1049 ◽  
pp. 355-361 ◽  
Author(s):  
Sanjima Pal ◽  
Mahesh Jadhav ◽  
Thomas Weyhermüller ◽  
Yogesh Patil ◽  
M. Nethaji ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Molecular Structures ◽  
Side Chain

scholarly journals Six New Lanostane Triterpenoids from the Fruiting Body of Tyromyces Sambuceus and Antiproliferative Activity

2016 ◽  
Vol 11 (2) ◽  
pp. 1934578X1601100
Author(s):  
Naoki Kokudo ◽  
Mina Okazoe ◽  
Joji Takahashi ◽  
Kanako Iseki ◽  
Kazuko Yoshikawa ◽  
...  
Keyword(s):  
Antiproliferative Activity ◽  
Fruiting Body ◽  
Heteronuclear Nmr ◽  
Human Cancer ◽  
Data Interpretation ◽  
Side Chain ◽  
X Ray ◽  
Human Cancer Cell Lines ◽  
Data Analyses ◽  
Nmr Data

During the search for secondary metabolites with antiproliferative activity, six new lanostane triterpenoids, tyrosamic acids A-F (1–6) together with ten known compounds (7–16), were isolated from the fruiting body of Tyromyces sambuceus. Their structures were elucidated using MS analyses, extensive 2D-heteronuclear NMR data interpretation and the structure of 3 was further confirmed by single-crystal X-ray data analyses. All lanostane triterpenoids (1–16) possesses a carboxy group at C-20 position and their strength of antiproliferative activity was affected by the presence or absence of a hydroxy group at C-15 position and at the side chain. Four of the compounds (1, 6, 10, 14) showed antiproliferative activities against human cancer cell lines with IC50 values of 16.8–48.3 μM (HL-60).

scholarly journals Novel (−)-goniofufurone mimics: Synthesis, antiproliferative activity and SAR analysis

2019 ◽  
Vol 84 (12) ◽  
pp. 1345-1353
Author(s):  
Bojana Sreco-Zelenovic ◽  
Sladjana Kekezovic ◽  
Mirjana Popsavin ◽  
Vesna Kojic ◽  
Goran Benedekovic ◽  
...  
Keyword(s):  
Cell Line ◽  
Cell Lines ◽  
Antiproliferative Activity ◽  
Malignant Cell ◽  
Side Chain ◽  
Antiproliferative Effects ◽  
Antitumour Agent ◽  
Sar Analysis ◽  
Human Tumour Cell Lines

Divergent syntheses of novel (?)-goniofufurone mimics with an alkoxymethyl group as the side chain have been accomplished from D-glucose in nine synthetic steps and in overall yields 6.7?8.7 %. Their in vitro antiproliferative activity was evaluated against eight human tumour cell lines as well as a single normal cell line. All analogues demonstrated powerful to good antiproliferative effects toward all malignant cell lines under evaluation. Against the HL-60 cell line, all mimics showed increased activities being 27- to 1604-fold more potent than the lead compound, (?)-goniofufurone. Remarkably, the majority of synthesized analogues displayed higher or similar activity to the commercial antitumour agent doxorubicin (DOX) against A549 cell line. The most potent compound exhibited 196-fold stronger cytotoxicity than DOX in the culture of this cell line.

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