Anticancer, antioxidant activities, and DNA affinity of novel monocationic bithiophenes and analogues

Abstract

A series of 15 monocationic bithiophenes and isosteres were prepared and subjected to in vitro antiproliferative screening using the full National Cancer Institute (NCI)-60 cell line panel, representing nine types of cancer. Among the nine types of cancer involved in a five-dose screen, non-small cell lung and breast cancer cell lines were the most responsive to the antiproliferative effect of the tested compounds, especially cell lines A549/ATCC, NCI-H322M, and NCI-H460, whereas compounds 1a, 1c, 1d, and 7 exhibited potent activity, with GI50 values (drug concentration that causes 50% inhibition of cell growth) from less than 10 nM to 102 nM. In addition, compounds 1c and 1d gave GI50 values of 73 nM and 79 nM, respectively, against the MDA-MB-468 breast cancer cell line. Structure–activity relationship findings indicated that the mononitriles were far less active than their corresponding monoamidines and, within the amidines series, the bioisosteric replacement of a thiophene ring by a furan led to a reduction in antiproliferative activity. Also, molecular manipulations, involving substitution on the phenyl ring, or its replacement by a pyridyl, or alteration of the position of the amidine group, led to significant alteration in antiproliferative activity. On the other hand, DNA studies demonstrated that these monoamidine bichalcophenes have promising ability to cleave the genomic DNA. These monoamidines show a wide range of DNA affinities, as judged from their DNA cleavage effect, which are remarkably sensitive to all kinds of structural modifications. Finally, the novel bichalcophenes were tested for their antioxidant property by the ABTS (2,2′-azino- bis(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt) assay, as well as lipid and nitric oxide scavenging techniques, and were found to exhibit good-to-potent antioxidant abilities.

Synthesis and Biological Evaluation of Bisthiazoles and Polythiazoles

“…The increase in nuclease-like activities of compound 1 may be due to the electron withdrawing activity of the sulfonyl moiety and the negative inductive effect of two Cl atoms, which lie between C=O and =N–N–H as electron donating groups. The results of DNA degradation by the tested compounds was in agreement with that formerly stated [ 31 , 32 , 33 , 34 , 35 ]. In conclusion, the present study proves that the compounds have substantial DNA digestion abilities, in the absence of external materials, at 10 µg.…”

“…This may be owing to the existence of N and S atoms in the tested compound. It has been proposed that the compounds that have N and S atoms might repress enzyme activity, since enzymes which require certain clusters for their activity are especially susceptible to deactivation by the tested compounds [ 32 ].…”

Experimental and theoretical studies on corrosion inhibition of 4-amidinophenyl-2,2′-bifuran and its analogues in acidic media

“…The tested bichalcophenes in this manuscript have been recently reported for their signicant DNA-binding affinity, 9 antibacterial, 10 antimutagenic, 11 and antiproliferative activities. 12 In addition, bifuran derivative MA-0947 was proven to be more effective than vancomycin against methicillin-resistant Staphylococcus aureus infection in mice. 13 Surface examination was conducted by atomic force microscopy (AFM).…”

Synthesis, antimicrobial, and antiproliferative activities of substituted phenylfuranylnicotinamidines

“… 14 – 17 Recently, several aryl-2,2′-bichalcophene monoamidines, including their aza-analogs, were synthesized and shown to exhibit potent antibacterial, 18 – 20 antimutagenic, 21 , 22 and anticancer activities. 23 …”