Synthesis, anticancer activities and molecular modeling studies of novel indole retinoid derivatives

Abstract

a b s t r a c tIn this study, novel (E)-3-(5-substituted-1H-indol-3-yl)-1- (5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)prop-2-en-1-one (5(aee)) derivatives were synthesized and their anticancer effects were determined in vitro. Novel indole retinoid compounds except 5e have anti-proliferative capacity in liver, breast and colon cancer cell lines. This anti-proliferative effect was further analyzed in breast cancer cell line panel by using the most potent compound 5a. It was determined that 5a can inhibit proliferation at very low IC 50 concentrations in all of the breast cancer cell lines. Here, we present some evidence on apoptotic termination of cancer cell proliferation which may be primarily driven by the inhibition of RXRa and, to a lesser extent, RXRg.

Electrosprayed poly(butylene succinate) microspheres loaded with indole derivatives: A system with anticancer activity

“…Thus, a differential effect against cancer cells and immortalized cells is deduced. This observation is in full agreement with other reported studies that justified the differential sensitivity of cancer cells in base on the expression of a gene pool [34]. Specifically, a new indole retinoid derivative had a high antiproliferative effect against 11 breast cancer cell lines, whereas a similar effect on immortalized normal breast cell line (MCF-12A) required a fourfold higher concentration than its IC 50 value.…”

“…The indole core has been deemed as an important moiety found in many pharmacologically active compounds (Table 1). These possess certain biological features such as anticancer effectiveness [34][35][36][37][38][39][40][41] and antiviral activity [42]. Furthermore, indole derivatives have the unique property of mimicking the structure of peptides and reversibly bind enzymes [43,44].…”

Retinoic acid signaling pathways in development and diseases

“…Compound 33 showed significant activity especially in breast cancer cell lines, including estrogen receptor (ER)-positive and ER-negative cell lines. 102 …”

Some new indole–coumarin hybrids; Synthesis, anticancer and Bcl-2 docking studies

“…Amidst them, heterocycles with polycyclic ring system possess distinct rigid geometry displaying high functional specialization by orienting its substituents in three dimensional spaces, there by attracting great interest [2]. Indole is a bicyclic heterocyclic scaffold that find applications in medical therapy due to a variety of valuable biologic activities such as antiviral [3,4], antiinflammatory [5,6], anti-hyperlipidemic, antihypoglycemic, anti-hypertensive, anti-asthmatic, anti HIV [7], antidepressant [8] and notably anticancer [9][10][11][12][13][14][15] activity. Few marketed anticancer indole derivatives are vincristine, vinblastine, vinorelbine, vindesine, mitraphylline, cediranib and apaziquone [2].…”