Thiophene Derivatives as New Anticancer Agents and Their Therapeutic Delivery Using Folate Receptor-Targeting Nanocarriers

Abstract

A series of thiophene derivatives were synthesized by functionalization of 2,3-fused thiophene scaffolds. Their cytotoxicity was assessed against HeLa and Hep G2 cells. Compound 480 was identified as a promising candidate because of its low IC 50 in HeLa (12.61 μg/mL) and Hep G2 (33.42 μg/mL) cells. The drug was loaded into folic acid (FA)-coated nanoparticles (NPs) to address its poor water solubility and to improve its selectivity for cancer cells. Compound 480 was shown to induce apoptosis by changes in mitochondrial membrane potential (ΔΨ m ) and the reactive oxygen species level. Furthermore, FA-modified NPs enhanced uptake capacity compared to unmodified controls by flow cytometry. This drug delivered in folate nanocarriers is promising for the treatment of cancers.

Identification of potential descriptors of water-soluble fullerene derivatives responsible for antitumor effects on lung cancer cells via QSAR analysis

“…Thiophene is a monocyclic heteroarene that consists of sulfur atom in a planar five-membered heterocyclic ring [65] . The thiophene moiety is commonly present in various thiophene-based drugs including nonsteroidal anti-inflammatory (NSAID), antihistaminic, antiasthma, and antitumor drugs [66] , [67] . Therefore, thiophene derivatives are an important class of heterocyclic compounds in the field of medical applications.…”

Toxicity and Antitumor Activity of a Thiophene–Acridine Hybrid

“…The clinical use of acridine and thiophene compounds is limited by problems such as side effects, drug resistance, and low bioavailability, which have encouraged further modifications of these compounds [14,22]. Previous data have shown cytotoxicity of acridine compounds, including amsacrine, against peripheral blood mononuclear cells (PBMC) [23].…”

“…Nevertheless, the clinical usefulness of acridine and thiophene compounds is limited due to the risk of high toxicity and drug resistance [14,15]. Moreover, the research and development of new alternatives for cancer treatment is necessary to provide a greater response to the tumor with less toxicity.…”

Synthesis, Pharmacological Evaluation, and In-Silico Studies of Thiophene Derivatives

“…ROS is known to induce a variety of human malignancies, and given the severity of the disease, the anticancer profile of thiophene-based compounds has mostly been thoroughly studied [41][42][43][44][45][46]. The present research was carried out as an outcome of this finding to design strong RORγt inhibitors via the introduction of various substituted aromatic moieties at the thiophene terminal (Scheme 1) and assess their therapeutic potential to continue our search for novel anticancer agents.…”