Synthesis and Antitumor Activity of Mechercharmycin A Analogues

Abstract

The cytotoxicity of 1 and the synthesized analogues were evaluated against a panel of three human tumor cell lines. Thiopeptide 1 and the most active derivatives 2 and 3c were chosen for further studies on effects on cell cycle progression and induction of apoptosis. Interestingly, the inhibition of cell division and activation of a programmed cell death by apoptosis were detected.

Palladium-catalyzed coupling reactions for the preparation of concatenated azoles

“…Several coupling reactions were tried without detection of 2-(4-bromothiazol-2-yl)oxazole. The formation of small amounts of the 2,2'-bisoxazole was detected using Pd(OAc) 2 and PPh 3 but we did not have any signs of achieving a coupling reaction with 2,4-dibromothiazole (see experimental procedure).…”

“…A great effort has been put into the synthesis of oxazole-containing compounds, because of the broad spectrum of biological activity. [1][2][3][4] Transition metal-catalyzed cross-coupling reactions have emerged as a powerful synthetic tool that allows a wide range of cross-coupling partners to be combined efficiently. 5 This method has been used for C-C bond formation in many synthetic procedures.…”

Predicting the unpredictable: Recent structure–activity studies on peptide-based macrocycles

“…HCT-116 -resistant colon carcinoma. [54]. A closely related linear metabolite to M1, Mechercharmycin B (Fig.…”

“…Taken together, these data showed that the macrocyclic structure was vital for the cytotoxicity of the molecule. Alvarez and co-workers built an SAR of M1 by first inserting methyl substituents on up to two of the oxazoles to increase the molecules solubility over the non-methylated version, and to induce a conformational change to the macrocycle (M2-M4, Table 3) [54]. Placing a methyl substituent on either R 1 or R 2 on Structure A (M1 analogues) lowered the inhibitory effect of the macrocycle by P10-fold compared to that of M1 on three different types of carcinoma.…”

Synthesis of Macrocyclic Hexaoxazole (6OTD) Dimers, Containing Guanidine and Amine Functionalized Side Chains, and an Evaluation of Their Telomeric G4 Stabilizing Properties

“…Trioxazoles 4 and 6 were synthesized starting with L-serine and L-lysine, respectively by using the previously reported procedure [29, 30, 36–38]. The Cbz group of 4 was removed by treatment with hydrogen in the presence of Pd(OH) 2 /C to give amine 5 .…”