In recent years, researchers like medicinal chemists in the field of medicinal chemistry have widely utilized the 1,3,4-thiadiazole nucleus to investigate its biological and pharmacological effects. This heterocyclic structure has demonstrated various bioactivities such as antifungal, antimicrobial, antiviral, antileishmanial, anti-inflammatory, antihypertensive, antiepileptic, and anticancer effects among others. Anticancer activity is one of its promising effect as five membered heterocyclic rings have widely been investigated by researchers in the recent years. Herein, we reviewed the chemical structures bearing 1,3,4-thiadiazole template exerting anticancer activity.
BackgroundAlzheimer’s disease (AD) as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh) concentration in hippocampus and cortex areas of the brain is one of the main reasons for this disease. In recent years, acetylcholinesterase (AChE) inhibitors like donepezil with prevention of acetylcholine hydrolysis can enhance the duration of action of acetylcholine in synaptic cleft and improve the dementia associated with Alzheimer’s disease.ResultsDesign, synthesis and assessment of anticholinesterase activity of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives showed prepared compounds can function as potential acetylcholinesterase inhibitor. Among 12 synthesized derivatives, compound 4a with ortho chlorine moiety as electron withdrawing group exhibited the highest potency in these series (IC50 = 0.91 ± 0.045 μM) compared to donepezil (IC50 = 0.14 ± 0.03 μM). The results of the enzyme inhibition test (Ellman test) showed that electron withdrawing groups like Cl, F and NO2 can render the best effect at position ortho and para of the phenyl ring. But compound 4g with methoxy group at position 3(meta) afforded a favorable potency (IC50 = 5.5 ± 0.7 μM). Furthermore, docking study confirmed a same binding mode like donepezil for compound 4a.ConclusionsSynthesized compounds 4a-4l could be proposed as potential anticholinesterase agents.
A new series of 4-aryl-4H-chromenes bearing a 2-arylthiazol-4-yl moiety at the 4-position were prepared as potential cytotoxic agents. The in-vitro cytotoxic activity of the synthesized 4-aryl-4H-chromenes was investigated in comparison with etoposide, a well-known anticancer drug, using MTT colorimetric assay. Among them, the 2-(2-chlorophenyl)thiazol-4-yl analog 4b showed the most potent activity against nasopharyngeal epidermoid carcinoma KB, medulloblastoma DAOY, and astrocytoma 1321N1, and compound 4d bearing a 2-(4-chlorophenyl)thiazol-4-yl moiety at the 4-position of the chromene ring exhibited the best inhibitory activity against breast cancer cells MCF-7, lung cancer cells A549, and colon adenocarcinoma cells SW480 with IC(50 )values less than 5 microM. The ability of compound 4b to induce apoptosis was confirmed in a nuclear morphological assay by DAPI staining in the KB and MCF-7 cells.
In the current research of medicinal chemistry, apoptosis induction is one of the novel strategies for the development and discovery of novel anticancer therapeutics. In the present study, a new series of 1,3,4-thiadiazole derivatives (4a-4p) were synthesized and their in vitro anticancer activities were evaluated against three cancer cell lines: PC3 (prostate cancer), MCF7 (breast cancer), and SKNMC (neuroblastoma). These cell lines were utilized in MTT assays and the obtained results were compared to doxorubicin. Apoptosis induction was also investigated through exploration of the activation of caspases 3, 8, and 9. According to the obtained results, compounds 4b (3-Cl) and 4c (4-Cl) demonstrated the best caspase activation. In fact, compounds 4b and 4c enhanced the activity of caspases 3 and 9 in the MCF7 cell line.
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