Abstract
Conjugates of naphthalimide, benzothiazole, and indole moieties are synthesized that show excellent cytotoxicity against A549 (lung), MCF7 (breast), and HeLa (cervix) cancer cell lines with IC50 values in the range of 0.14–8.59 μM. Compounds 12 and 13 substituted with ethanolamine and propargyl groups reveal potent cytotoxicity towards A549 cancer cells with IC50 values of 140 and 310 nM, respectively. These compounds are further evaluated as potent inhibitors of human type IIα topoisomerase. These conjugates also reveal strong interaction towards human serum albumin (HSA) with binding constant values of 1.75 × 105 M−1 and 1.88 × 105 M−1, respectively, and formation of the stable complex at ground state with static quenching. Docking studies also confirm the effective interactions between conjugates and topoisomerase.
Highlights
With climate change, cancer is becoming a major problem in public health
Compounds 7–22 were tested for their cytotoxicity against A549, MCF7, and HeLa human cancer cell lines at 1, 10, and 100 mM concentrations
The results indicated that these compounds altered the human serum albumin (HSA) con rmation so that a decrease in polarity near tyrosine residue while increasing the polarity around tryptophan residue was depicted
Summary
Cancer is becoming a major problem in public health. Cancer can be described as the abnormal and uncontrolled growth of cells which spread to nearby organs via the circulatory system. A standard antitumor drug should selectively express cytotoxicity for cancer cells without harming normal cells; otherwise, it may lead to severe side effects. Existing cancer therapies, i.e., radiotherapy, surgery, and chemotherapy, are becoming ineffective due to multidrug resistance. Naphthalimide, a heterocyclic moiety, is a group of wellestablished antiproliferative agents, and some derivatives (amona de, mitona de, and UNBS5162) have reached different phases of clinical trials.. Naphthalimide, a heterocyclic moiety, is a group of wellestablished antiproliferative agents, and some derivatives (amona de, mitona de, and UNBS5162) have reached different phases of clinical trials.9,10 Another heterocyclic moiety, benzothiazole-based compounds, were reported to show. These hybrids indicated higher antiproliferative activity than the clinical trial drug, amona de These previous results concluding the improved cytotoxicity of conjugates of naphthalimide and benzimidazole moieties. Vincristine and vinblastine are the indole-based inhibitors of tubulin protein that increase the importance of indole scaffold in the eld of cancer.26,27 These conjugates were synthesized possessing variable substituents, which were planned to achieve the aim of target cytotoxicity. The docking studies were performed to con rm their interactions with TOPO IIa
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