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Introduction
Cervical cancer and melanoma are aggressive cancers with increasing incidence worldwide (1). Whereas cervical cancer ranks fourth cancer for both incidence and mortality, malignant melanoma is the most serious type of skin cancer and accounts for the majority of skin cancer-associated mortalities (1,2). Cervical cancer is commonly treated with a combination of radiotherapy and platinum-based chemotherapy, which may also damage normal cells (3). At present, there is no globally accepted standard treatment that offers a significant survival benefit for patients with advanced-stage melanoma (2). Until 2011, the chemotherapeutic drugs dacarbazine, temozolomide and fotemustine were most commonly used for metastatic melanoma treatment (4); however, only a low percentage of patients who received these compounds exhibited a significant response. These treatments have been mostly replaced by the immune-checkpoint inhibitors, including cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), B-Raf proto-oncogene (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors (5). However, these therapeutic alternatives display adverse events, including secondary cutaneous squamous cell carcinomas and keratoacanthomas, which occur in ~20% of patients treated with BRAF-inhibitor (6). A previous study reported that MEK inhibitors have more serious adverse effects and a lower efficacy compared with BRAF inhibitors (5). The development of novel effective agents for the treatment of these cancers is therefore crucial.
Imidazopyridines possess a wide range of biological activities. In particular, the imidazo[1,2-a]pyridine moieties of imidazopyridine have recently gained significant interest as potential anticancer agents due to their potent inhibitory role of cancer cell growth, which is commonly due to survival kinases inhibition (7,8). Various drugs containing imidazo[1,2-a]pyridine moieties are currently used to treat cardiac disorders, insomnia, antianxiety, ulcers and HIV infections (9). Although these compounds have numerous medicinal applications, none of them have been accepted as an anti-cancer drug. However, previous studies have reported that imidazo[1,2-a]pyridines have some anti-cancer abilities. For example, Goel et al (9) recently reported that 3-{1-[(4-fluorophenyl)sulfonyl]- 1H-pyrazol- 3-yl}-2-methylimimoredazo[1,2-a]pyridine may be a novel PIK3CA inhibitor with an half maximal inhibitory concentration (IC50) of 0.67 µM. Further optimization of the substituents resulted in thiazole groups substituted by imidazo[1,2-a]pyridines, which are more potent inhibitor of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PI3KCA) with an IC50 of 0.0028 µM (10). In addition, this compound exerts a promising anti-proliferation effect against melanoma (A375) and cervical (HeLa)...