Anticancer and Immunomodulatory Activities of a Novel Water-Soluble Derivative of Ellipticine

Abstract

Cancer still remains a major public health concern around the world and the search for new potential antitumor molecules is essential for fighting the disease. This study evaluated the anticancer and immunomodulatory potential of the newly synthetized ellipticine derivate: sodium bromo-5,11-dimethyl-6H-pyrido[4,3-b]carbazole-7-sulfonate (Br-Ell-SO3Na). It was prepared by the chlorosulfonation of 9-bromoellipticine. The ellipticine-7-sulfonic acid itself is not soluble, but its saponification with sodium hydroxide afforded a water-soluble sodium salt. The cytotoxicity of Br-Ell-SO3Na was tested against cancerous (K562 cell line) and non-cancerous cells (Vero cell line and human peripheral blood mononuclear cells (PBMC)) using a Methylthiazoletetrazolium (MTT) assay. Cell cycle arrest was assessed by flow cytometry and the immunomodulatory activity was analyzed through an enzyme-linked immunosorbent assay (ELISA). The results showed that the Br-Ell-SO3Na molecule has specific anticancer activity (IC50 = 35 µM) against the K562 cell line, once no cytotoxicity effect was verified against non-cancerous cells. Cell cycle analysis demonstrated that K562 cells treated with Br-Ell-SO3Na were arrested in the phase S. Moreover, the production of IL-6 increased and the expression of IL-8 was inhibited in the human PBMC treated with Br-Ell-SO3Na. The results demonstrated that Br-Ell-SO3Na is a promising anticancer molecule attested by its noteworthy activity against the K562 tumor cell line and immunomodulatory activity in human PBMC cells.

In-Silico Study: Potential Inhibitor of Cyclin-Dependent Kinase 6 (CDK6) from Natural Plant Compounds for Melanoma Treatment

“…Hopefully, this study could be used as the basis for both in-vivo and in-vitro studies, hence new herbal plant-based therapies can be found for treating melanoma. Ochrosia vieillardii, Ochrosia acuminata, Ochrosia moorei, Strychnos dinkagei, and families of Apocynaceae 23,24…”

Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma

“…Furthermore, using electron microscopy, the authors showed further ultrastructure changes due to apoptosis activation by EPED3 on MM cells, such as the destruction of mitochondrial inner cristae, nuclear pyknosis, and formation of multiple cytosolic vacuoles, hoping for its use in vivo as an antimyeloma agent in combination with conventional drugs [ 62 ]. However, in vitro studies are still ongoing regarding the identification of other effective water-soluble derivatives of Ellipticine, such as anticancer agents and immunomodulators for its low bioavailability [ 63 ].…”

Rational Optimization of 1,2,3-Triazole-Tailored Carbazoles As Prospective Antibacterial Alternatives with Significant In Vivo Control Efficiency and Unique Mode of Action

“…6,14−17 The advances in the chemical modification of natural products have highly motivated the discovery and development of new pesticides or pharmaceuticals. 18−23 In particular, chemically modified carbazole derivatives augment biological silhouettes and display antimicrobial, 24,25 anticancer, 26,27 antiinflammatory, 28,29 antiproliferative, 30,31 antituberculosis, 32,33 and anti-Alzheimer effects. 34,35 Because of the distinctive electronic and charge-transport performance of this privileged carbazole skeleton, the molecular design and engineering based on this scaffold and the underlying mechanism of action were continuously investigated.…”

“…The advances in the chemical modification of natural products have highly motivated the discovery and development of new pesticides or pharmaceuticals. − In particular, chemically modified carbazole derivatives augment biological silhouettes and display antimicrobial, , anticancer, , anti-inflammatory, , antiproliferative, , antituberculosis, , and anti-Alzheimer effects. , Because of the distinctive electronic and charge-transport performance of this privileged carbazole skeleton, the molecular design and engineering based on this scaffold and the underlying mechanism of action were continuously investigated. , In our previous work, we developed a type of 9-substituted carbazole derivative bearing an isopropanolamine linker as an antibacterial compound against plant pathogens. We found that the rational modification of the carbazole nucleus can arouse and advance the discovery of more effective ingredients that can be used in the control of bacterial diseases .…”