Three thienylpicolinamidine derivatives 4a–c were prepared from their corresponding picolinonitriles 3a–c on treatment with lithium trimethylsilylamide, LiN(TMS)2, followed by a de-protection step using ethanol/HCl (gas).

Twelve new thienylbenzamidines and their analogues 4 a-i, 7, and 12 a, b were synthesized and their anti-proliferative activity was evaluated against 60 cancer cell lines. The tested compounds showed potent anticancer activity against most cancer cell lines with median growth inhibition (GI 50 ) < 2 μM. Leukemia and renal cancer cell lines were the most responsive. Compound 12 a was the most active exhibiting GI 50, total growth inhibition (TGI), and median lethal concentration (LC 50 ) at 1.65, 3.71, and 9.3 μM, respectively. The benzamidine derivatives exerted their anti-proliferative activity without causing any toxicity in normal human lung fibroblast (WI-38) cells. The selectivity index (SI) ranged from 5.6 to 59.0 fold. Compound 4 h was the most selective compound (SI = 59), and it was the least cytotoxic to WI-38 cells. The cationic compounds 4 c, 4 h, 4 i, 7, and 12 b with high SI were selected for further mechanistic studies. Compounds 4 c, 4 h, and 4 i exerted their antiproliferative activity by inducing the cell cycle arrest (elevated p53 and downregulated cyclin-dependent kinase 1 (cdk1)) and inducing apoptosis (elevated caspase 3). Compounds 7 and 12 b exerted their activity by inhibiting the growth and proliferation of cancer cells through inhibiting both topoisomerase II (topoII) and thioredoxin reducta-se1 (txnrd1). Finally, in silico predictions of the physicochemical, pharmacokinetic and drug-likeness profiles of these new derivatives proved the oral availability and the inability to cross the blood-brain barrier.

We have synthesized new metal-free dyes (HB-1–8) containing bifuran/biphenyl derivatives for dye-sensitized solar cells. Dye HB-3 exhibited the highest efficiency among the eight investigated dyes, reaching 5.51% with a VOC value higher than N3.