Small molecule induces mitochondrial impairment in colon cancer cells

Abstract

Mitochondrion is one of the most important organelles controlling multiple diverse biological phenomena. Consequently, dysfunction in mitochondria leads to the initiation, development and progression of cancer, especially colon cancer. However,...

3‐Methoxy‐Pyrrole‐Based Small Molecule Damages Mitochondria to Instigate Apoptosis in Breast Cancer Cells

“…Moreover, this 3‐methoxy‐pyrrole killed drug resistant MDA‐MB‐231 triple negative breast cancer cells and OVCAR8 ovarian cancer cells. Interestingly, from the same 3‐methoxy‐pyrrole library, we identified compound 5 which showed remarkable cell killing ability in colon cancer cells while compound 3 showed much less cell killing effect with minute structural modifications [26] . On the other hand, in this work, we identified compound 3 which is capable of killing breast cancer cells while compound 5 showed much moderate ability to kill them.…”

“…Interestingly, from the same 3-methoxy-pyrrole library, we identified compound 5 which showed remarkable cell killing ability in colon cancer cells while compound 3 showed much less cell killing effect with minute structural modifications. [26] On the other hand, in this work, we identified compound 3 which is capable of killing breast cancer cells while compound 5 showed much moderate ability to kill them. This result clearly indicated that biological activity guided single focused library could generate lead molecules for the treatment of different types of cancers towards personalized chemotherapy regimen.…”

“…It was observed that compound 3 remarkably suppresses viability of OVCAR8 cells with IC 50 = 8 μM compared to obatoclax (Figure S3, Table S1). The structure of compound 3 was characterized previously by using 1 H, 13 C NMR spectroscopy and HR-MS. [26] To confirm the geometry of olefin in compound 3, we performed 2-dimensional correlation spectroscopy (COSY) which showed the interaction of H c with H b and H d as well as the interaction between H g and H f aromatic protons confirming the chemical shift of H a = 6.93 ppm (Figure S4). Further 2-dimensional Nuclear Overhauser Enhancement Spectroscopy (NOESY) revealed that H a interacted through space with H b and H e (Figure S5) which is only possible if the geometry of the olefin is Z.…”

“…We have synthesized the library of 3-methoxy-pyrrole (13 compounds) through a concise synthetic strategy (Figure 1b and Figure S1). [26] To find out the lead molecule, we treated triple negative breast cancer cells (MDA-MB-231) by the library members in a dose dependent manner for 48 h. Obatoclax was used as a positive control for this assay. The cell viability assay showed that compound 3 induced 26 % cell viability at 100 μM concentration with IC 50 value = 9 μM (Figure S2, Table S1), which is very comparable with the IC 50 value of the obatoclax (IC 50 = 9 μM).…”

Small‐Molecule Endoplasmic Reticulum Stress Inducer Triggers Apoptosis in Cancer Cells

“…Finally, compounds 4 a–e were condensed with mono‐tosylated ethylenediamine (5 a) and mono‐dansylated ethylenediamine (5 b) in presence of catalytic acetic acid to obtain 3‐methoxy‐pyrrole enamines (6 a–i) in 79–89 % yield (Figure S3). The new aldehyde (4 e, Figure S2) and all the library members were characterized by 1 H, 13 C NMR and HR‐MS spectroscopy (Figure S4–S33) [32,33] …”