Jul 2026· International Journal of Drug Delivery Technology· Vol 16· 0 citations· 31 references
TL;DR
The flow cytometric analysis demonstrated that compound 5E caused cells to undergo apoptosis while blocking their normal cell cycle progression, which resulted in an increased SubG1 population.
Abstract
The research includes all stages of development, which include designing, synthesizing,
molecular docking work, and testing anticancer properties of imidazo[2,1-b]thiazole
compounds (5A–5E). The molecular docking studies showed that the complex formed
between the two proteins displayed strong binding capacity to epidermal growth factor
receptor and estrogen receptor alpha. The researchers used the MTT assay to test the
cytotoxic activity of synthesized compounds against MCF-7 and MDA-MB-231 cell lines,
which demonstrated that cell viability decreased with increasing concentration. The
compound 5E showed the strongest cytotoxic properties among all tested compounds, while
5C displayed the second-highest activity level based on its lowest IC₅₀ value. The flow
cytometric analysis demonstrated that compound 5E caused cells to undergo apoptosis while
blocking their normal cell cycle progression, which resulted in an increased SubG1
population. The studies revealed that compound 5E served as the main lead candidate for
development as an anticancer drug.
Structural–activity relationship analysis revealed the importance of the TZD core, electron-rich aromatic moieties, and balanced lipophilicity for enhanced anticancer activity, identifying TZD hybrids as promising EGFR-targeted anticancer leads.
Rajyalaxmi Injamuri, D. Makula· International journal of res...· 0 citations
A novel set of imidazo[2,1-b]thiazolediones 4a,b and 5a-d, with anticipated EGFR and IDO1 inhibition activities, was designed and prepared. These novel derivatives were evaluated in the NCI 60 cell line panel in which the superior compounds 5b and 5d were chosen for further evaluation of their five dose cytotoxicity toward the most sensitive cancer cells namely non-small cell lung cancer EKVX and HOP-92, breast HS 578 T, and normal WI-38 cells. The presence of a substituted benzylidene moiety at position-2 of the imidazothiazole scaffold in compounds 5a-d positively influences anticancer activity, with the phenylallylidene moiety at position-6 exhibiting superior cytotoxic effects compared to the 2-thienylidene moiety. Among the examined hybrids, 5d showed significant antiproliferative effect against HS 578 T tumor cell. To explore the underlying cell-death mechanisms, secondary biological evaluations were conducted, including cell-free EGFR and IDO1 enzymatic inhibition, apoptosis assay, and cell cycle analysis. In cell-free biochemical assays, the most active derivatives demonstrated a promising potential dual inhibitory profile against EGFR and IDO1, with compound 5d exhibiting sub-micromolar activity against both target enzymes, providing a plausible biochemical rationale for its potent cell killing. Furthermore, compound 5d induced cell cycle arrest at the G2/M phase and triggered apoptosis in HS 578 T cells, as supported by the up-regulation of Caspase-3 and Bax accompanied by the down-regulation of Bcl-2. In-silico ADMET profiling and molecular docking simulations further supported the favorable drug-like properties and binding modes of the key compounds within the target active sites. Overall, these findings highlight compound 5d as a promising lead candidate for further optimization and cellular mechanistic validation in anti-cancer drug discovery.
M. Sarg, Fatma G. Abdulrahman, Yasmin S. Sheta et al.· Bioorganic & Medicinal Chemi...· 0 citations
The present work describes the synthesis, molecular docking, and preliminary anticancer evaluation of a hybrid compound, product-
C
composed of a fluorinated sulfur heterocyclic core and an adamantane moiety. The synthesis method was designed to tune the electronic, lipophilic and structural properties of the compound through the introduction of CF₃, F and Cl functional groups, which are well known for the improving metabolic stability, physicochemical properties and drug-likeness. The structure of the synthesized compound was confirmed by
1
H and
13
C nuclear magnetic resonance (NMR) spectra. Molecular docking against phosphoinositide 3-kinase (PI3K), a protein target implicated in multiple cancers, showed that product-
C
exhibited a binding affinity of -10.6 kcal/mol, suggesting favorable interaction with the target. In parallel, the SRB (Sulforhodamine B) assay was used to evaluate the cytotoxicity of product-
C
toward PANC-1 cells. Preliminary results showed cell viabilities of 98.86% and 95.55% after exposure to 10 μM and 100 μM of product-
C
, respectively. These findings indicate that product-
C
displays low cytotoxicity toward PANC-1 cells under the tested conditions; however, they do not by themselves demonstrate marked antiproliferative activity.
M. Alamri, Yassine Riadi, A. Altharawi et al.· Arabian Journal of Chemistry· 0 citations
Mechanistic studies indicated that compounds 5c and 5f inhibited cancer cell growth predominantly by inducing apoptosis rather than cell cycle arrest, indicating favourable selectivity.
Rachel Alveera Menezes, Navas Shereef Ellyan, M. M. et al.· RSC Advances· 0 citations
We herein report the anticancer activity and molecular docking studies of a series of amide derivatives of two nonsteroidal anti-inflammatory drugs (mefenamic acid and ibuprofen). The hypothesis of drug repurposing has been successfully employed to explore the promising anticancer activity of analogs of known anti-inflammatory agents. The compounds have been tested for their inhibitory potential against cervical cancer cell lines by MTT assay using 5-fluorouracil as the reference standard. Among the compounds screened, 3aa [2-(2,3-dimethylamino)phenyl)(1H-indol-1-yl)methanone] and 3ad [2-(2,3-dimethylphenylamino)phenyl)(9H-carbazol-9-yl)methanone] displayed good potency of less than 25 µg/mL half-maximal inhibitory concentration (IC50). The docking analysis has confirmed that molecule 3aa effectively binds to the active site of the target protein CDK2, with a docking score of −9.21 Kcal/mol and a binding energy of −46.44 Kcal/mol, involving a hydrogen bond with Ile 10. The molecule 3ad also exhibited a good glide score of −6.78 Kcal/mol with the binding energy of −45.90 Kcal/mol. As many of the tested compounds displayed promising potency against cervical cancer cell lines, our investigation revealed the importance of drug repurposing in the development of lead molecules in medicinal chemistry.
Nivedya Prasad SreeNilayam, J. Abhithaj, S. Remeshan et al.· Biophysica· 0 citations
The results revealed that the synthesised derivative 3h has potential binding affinity hence blocking the activity, and the synthesised piperazine derivatives are identified as promising lead compounds for further anticancer optimization.
Vaibhav Daund, Pooja Agarwal, A. Jain et al.· Asian Journal of Chemistry· 0 citations
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