A novel series of benzimidazole-naphthalimide conjugates was synthesized for the first time and screened for in vitro biological activity for 60 human cancer cell lines representing nine different cancer types.
Besides worthy development in cancer therapy, cancer is still one of the leading causes of death, worldwide. The future burden of cancer will probably be even larger because people are adopting poor lifestyles with poor diet, frequently smoking and less physical activity. The effective anticancer drugs having efficacy and selectivity with low toxicity is still a challenge for the scientific fraternity. The advances in the cancer study have its origin on the availability of different types of experimental model systems that review the various forms of this disease. Cell lines emerge as a feasible alternative for anticancer activities, being at the same time easy to manipulate and molecularly characterize. Heterocycles are key structural components of many of the anti-cancer drugs available on the market today. Indeed, of the novel molecular anti-cancer agents approved by the FDA between 2010 and 2017, almost two-thirds contained heterocyclic rings within their structures. This review summarizes and provides updated literature on heterocyclic compounds using various cancer cell lines reported during the period of 2014-2017 together with the structure-activity relationships.
Novel derivatives possessing imidazo[1,2-a]pyrazine and 1H-benzo[d]imidazole scaffolds were synthesized using Suzuki-Miyaura cross-coupling reactions. In vitro anticancer activities against NCI-60 cancer cell panels were tested at 10 µM concentration. The best results were obtained from substitution of two 1-cyclohexyl-1H-benzo[d]imidazole groups present at C-6 and C-8 positions of imidazo[1,2-a] pyrazine (31). Compound 31 was found to be cytotoxic against 51 cell lines and cytostatic against 8 cell lines with broad range of growth inhibitions (−98.48 to 98.86%). GI 50 value of compound 31 was found in the range of 0.80-2.87 µM for 59 human cancer cell lines at five-dose concentration levels. DNA binding study of potent compound 31 was suggested that this compound was intercalated into DNA base pairs with binding constant of 1.25 × 10 4 M −1. Compound 31 showed effective binding with bovine serum albumin (BSA) and presented binding constant value of 3.79 ×10 4 M-1. Pharmacokinetic studies revealed that all compounds are following Lipinski's rule of five and expected to be orally active. Cancer is one of the major reasons for death globally. Millions of people suffer or die from cancer each year, and there is no particular good medication available at present 1. Cancer has significant economic impact, which is increasing gradually. In the field of cancer treatment, chemists have great challenges to discover new and efficient compounds with strong and broad-spectrum anticancer activity. Heterocyclic ring systems play significant role in the discovery of novel bioactive substances due to their minimal side effects and effective at small doses. Heterocyclic moieties are widely present in various natural bioactive compounds 2. Undesirable side effects, toxicity, drug resistance, and low bioavailability are some of the major known problems for currently available anticancer agents 3. Therefore, there is an urgent need for the discovery of more efficient and selective anticancer agent. The biological potential of these heterocycles towards cancer cells has been stated with diverse mechanism of action. Most of the anticancer candidates bind with DNA double-strand and interfere with replication and transcription, thus, interrupt DNA function and alter the cell division. These candidates show interaction between adjacent base pairs or bind with grooves of DNA. These candidates share similar structural features, for example, the presence of planarity in structure, which can help the molecule to bind with DNA through insertion between base-pairs. The basic chain connected with these heterocyclic moieties plays a significant role in the selectivity and affinity 4. Due to their high affinity, the discovery of novel DNA intercalator for cancer therapy is a crucial goal in the medicinal chemistry. These intercalators comprise anthracyclines 5,6 (e.g. doxorubicin and mitoxantrone), ellipticine 7 and acridine derivatives (e.g. amsacrine) 8 , used in the cancer therapy of acute leukemia, breast, and ovarian cancers. On account of r...
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