Synthesis of Novel Thiophene‐Chalcone Derivatives as Anticancer‐ and Apoptosis‐Inducing Agents

Abstract

A series of new thiophene linked chalcone hybrids has been designed and synthesized. The key intermediate thiophene‐2‐carbaldehyde 13 was synthesized by coupling furan and phenyl ring via Suzuki reaction. The new scaffolds were synthesized by base catalyzed condensation reaction from key intermediate with various substituted acetophenones to build the chalcone core. The conversion in this synthesis involves the following steps (i) Selective bromination, (ii) regioselective Suzuki coupling (iii) Various aromatic substituents were introduced by classical aldol condensation. We screened all compounds of this thiophene‐chalcone derivatives (15 a‐n) in selected cancer cell lines viz. Human breast (MCF‐7, MDA‐MB‐453) prostate cancer (PC‐3), lung (A549). The screened compounds showed good anticancer activity on two of the studied cell lines with best IC50 values of thiophene‐chalcone derivative 15 e (6.3±0.9 μM) on A549 and with GI50 values of compound 15 e (1.9±0.3 μM) on A549 cells. This strategy is operationally simple and works with a diverse range of substrates and warrants future investigations for further anticancer drug development.

Aryl‐Alcohol‐Oxidase‐Mediated Synthesis of Piperonal and Other Valuable Aldehydes

“…[24] 2-Thiophenecarboxaldehyde 3 b itself was used as building block for the synthesis of various anticancer-and apoptosis inducing compounds as well as in the production of thiophene-chitosan hydrogels, which facilitate removal of toxic heavy metal ions such as mercury from contaminated water with high efficiency. [25] Trans-2-cis-6-nonadienal 5 b (also termed as "violet leaf aldehyde" or "cucumber aldehyde") is among the most potent fragrance compounds and is found in aroma of various fruits and flower scents. [8,26] 10 and 100 mM of each 2 a, 3 a and 4 a were completely converted to the corresponding aldehydes within 20 h (Table 1, Figure S17-S19).…”

Synthesis, characterization, and molecular structure investigation of new tetrahydrobenzo[b]thiophene-based Schiff bases: A combined experimental and theoretical study

“…Certain thiophenes are known as potential inhibitors of D-amino acid oxidase [30], tyrosine phosphatase 1B [31], TNF-α [32], and carbonic anhydrase [33]. Moreover, a number of thiophenes have been employed as apoptosis inducing agents [34] and constitute the structural unit of a series of natural products [35]. Because of the importance of this heterocycle moiety, we became interested in the synthesis of new tetrahydrobenzo[b]thiophene-based Schiff bases.…”

Biological activity evaluation and action mechanism of chalcone derivatives containing thiophene sulfonate

“…[34][35][36] Therefore, thiophene sulfonate and its derivatives have a wide range of applications in industry, agriculture, pharmaceuticals and have a broad spectrum of biological activities, such as insecticidal, 37,38 anti-inammatory, 39,40 antiviral, 41,42 and anticancer. 43 However, to the best of our knowledge, there have been no reports on chalcone-based thiophene sulfonates so far. To nd excellent biological activities and environment-friendly small organic molecules, thiophene sulfonate structure with excellent biological activity is combined with the structure of chalcone by active splicing to design and synthesize a series of novel molecules.…”

“… 34–36 Therefore, thiophene sulfonate and its derivatives have a wide range of applications in industry, agriculture, pharmaceuticals and have a broad spectrum of biological activities, such as insecticidal, 37,38 anti-inflammatory, 39,40 antiviral, 41,42 and anticancer. 43 …”