2016
DOI: 10.1021/acsmedchemlett.6b00079
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Abstract: The polyether ionophore salinomycin has recently gained attention due to its exceptional ability to selectively reduce the proportion of cancer stem cells within a number of cancer cell lines. Efficient single step strategies for the preparation of hydroxamic acid hybrids of this compound varying in N-and O-alkylation are presented. The parent hydroxamic acid, salinomycin-NHOH, forms both inclusion complexes and well-defined electroneutral complexes with potassium and sodium cations via 1,3-coordination by the… Show more

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Cited by 29 publications
(19 citation statements)
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“…Importantly, this increase was recently shown to also translate to enhanced activity against CSC traits as demonstrated by both marker‐based and functional assays; selected 20‐ O ‐acylated analogues showed significant CSC activity already at 50 n m concentrations where salinomycin itself was inactive. Of mechanistic significance, we also recently showed that conversion of the carboxylate group to hydroxamic acid derivatives that strongly coordinates alkali metal ions but exhibit a decreased ionophore activity also lack activity against CSCs . Furthermore, a number of studies have been directed at biological and synthetic investigations of salinomycin .…”
Section: Introductionmentioning
confidence: 99%
See 1 more Smart Citation
“…Importantly, this increase was recently shown to also translate to enhanced activity against CSC traits as demonstrated by both marker‐based and functional assays; selected 20‐ O ‐acylated analogues showed significant CSC activity already at 50 n m concentrations where salinomycin itself was inactive. Of mechanistic significance, we also recently showed that conversion of the carboxylate group to hydroxamic acid derivatives that strongly coordinates alkali metal ions but exhibit a decreased ionophore activity also lack activity against CSCs . Furthermore, a number of studies have been directed at biological and synthetic investigations of salinomycin .…”
Section: Introductionmentioning
confidence: 99%
“…Of mechanistic significance,w ea lso recently showed that conversion of the carboxylate group to hydroxamic acid derivatives that strongly coordinates alkali metal ions but exhibit ad ecreased ionophore activity also lack activitya gainstC SCs. [7] Furthermore,anumber of studies have been directed at biological Figure 1. Structure, ion binding preference, andmode of complexf ormation of diverse polyethera ntibiotics, the oxygena toms providing coordination sites for ions (bold) and head-to-tail bonding (dashed lines) are indicated.…”
Section: Introductionmentioning
confidence: 99%
“…Alternatively, SAL, NIG and OBT may serve as lead compounds to develop derivatives more selective towards non-cancer cells. In this context, several derivatives of OBT [ 172 , 173 ] and SAL [ 120 , 121 , 174 , 175 , 176 , 177 , 178 , 179 ] have shown anticancer effects. For instance, derivatives with chemical modification of the allylic C20 hydroxyl of SAL, located at the C-ring, enhanced the activity over 5-fold against breast cancer cells compared to the native structure [ 121 ].…”
Section: Discussionmentioning
confidence: 99%
“…Because SAL exhibits so many diverse biological activities, there is significant interest in developing bioactive derivatives, especially since several SAL analogues examined to date exhibit superior biological activity than the parent structure . For example, our previous studies have indicated that derivatization of the C1 carboxylate moiety of SAL with amide, ester, or bioconjugate modifications generates compounds with higher potency and selectivity compared to commonly used chemotherapeutics, such as cisplatin or doxorubicin . Similarly, chemical modification of SAL at the C20 hydroxy group generates analogues superior to the starting compound …”
Section: Introductionmentioning
confidence: 99%
“…[22] For example, our previous studies have indicated that derivatization of the C1 carboxylate moiety of SAL with amide, ester, or bioconjugate modifications generates compounds with higher potency and selectivity compared to commonly used chemotherapeutics, such as cisplatin or doxorubicin. [23][24][25][26][27][28][29] Similarly, chemical modification of SAL at the C20 hydroxy group generates analogues superior to the starting compound. [30][31][32][33][34][35][36][37][38][39] We have recently exploited these findings to synthesize doubly modified SAL derivatives at the C1 and C20 positions that are highly promising anticancer agents both in vitro and ex vivo.…”
Section: Introductionmentioning
confidence: 99%