Catalyst free new bioactive 2‐amino‐4‐(2‐oxo‐2H‐chromen‐4‐yl)‐6‐arylpyridine‐3‐carbonitrile molecular entities (2 a‐2 o) have been synthesized from 4‐formylcoumarins with malononitrile, different ketones and ammonium acetate via one‐pot four component coupling reaction under neat microwave method. Detailed characterization of all the compounds and anticancer properties for the synthesized compounds are reported. Compounds 2 f and 2 k exhibited promising anticancer activity at low concentration (10−5 M) against NCI‐60 cell lines. Further, IC50 values were calculated for most potent compounds against three cancer cell lines such as HT‐29, Hep‐G2 and KB. Among the eight compounds, 2 f and 2 k are exhibited most promising activity, the potent anticancer molecules 2 f and 2 k were screened for their CT‐DNA cleavage and fluorescence quenching study with transport protein BSA. Molecular docking study has been performed for the synthesized compounds with binding site of the tubulin using podophyllotoxin‐tubulin stathmin‐like domain complex (PDB 1SA1) and results obtained are quite good.
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This review focuses on conventional treatment overview, signaling pathways and various reasons for drug
resistance with understanding novel methods that can lead to effective therapies. Ovarian cancer is amongst the most
common gynecological and lethal cancers in women from the age of 20-60. The survival rate is limited to 5 years due to
diagnosis in subsequent stages with reoccurrence of tumor and resistance of chemotherapeutic. The recent clinical trails
use combinatorial treatment of carboplatin and paclitaxel on ovarian cancer after cytoreduction of tumor. Predominantly
patients are responsive initially to therapy and later develop metastases due to drug resistance. Chemotherapy also leads to
drug resistance causing enormous variations at cellular level. Multifaceted mechanisms like drug resistance are associated
with number of genes and signaling pathways that process the proliferation of cells. Reasons for resistance include
epithelial-mesenchyme, DNA repair activation, autophagy, drug efflux, pathway activation, and so on. Determining the
routes on molecular mechanism that target chemoresistance pathways are necessary for controlling the treatment and
understanding efficient drug targets can open light on improve therapeutic outcomes. Most common drug used for ovarian
cancer is Cisplatin, which activates various chemoresistance pathways ultimately causing drug resistance. There have
been substantial improvements in understanding the mechanisms of cisplatin resistance or chemo sensitizing cisplatin for
effective treatment. Using therapies with combination that involve phytochemical or novel drug delivery system involving
the phytochemicals would be a novel treatment in cancer. Phytochemicals are plant-derived compounds that exhibit anticancer, anti-oxidative, anti-inflammatory properties that minimalize side effects exerted from chemotherapeutics.
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