Corresponding author: Vasyl Matiychuk (
The reaction of 1
Benzimidazoles and its derivatives are an important group of heterocyclic compounds that show a wide range of pharmacological properties such as antitumor, antimicrobial, antihypertensive, antiviral, antiulcer, anticonvulsant, antiinflammatory activities. Their widespread use as scaffolds in medicinal chemistry establishes this moiety as a member of the class of privileged structures (
On the other hand a detailed study of rhodanine (2-thioxo-4-thiazolidone) derivatives has made it possible to identify a lot of highly active agents with a wide range of biological activity. Among the 5-arylidenerhodanines, a lot of lead- compounds that possess various activities, including antimicrobial, antituberculous, antiviral, antidiabetic, anti-inflammatory, antitumor, anticonvulsant activities have been also found. At the present stage of development of medical chemistry, the rhodanine motif is considered to be also privileged (
These diverse biological applications of benzimidazole and rhodanine compounds have motivated new efforts in search for novel their hybrids derivatives with improved biological activity and diverse applications in pharmaceutical industry.
All chemicals were of analytical grade and commercially available. All reagents and solvents were used without further purification and drying. All the melting points were determined in an open capillary and are uncorrected.1H- spectra were recorded on a Varian Mercury 400 (400 MHz for 1H) instrument with TMS or deuterated solvent as an internal reference. Satisfactory elemental analyses were determined on a Elementar Vario L cube instrument (C±0.17, H±0.21, N±0.19).
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Primary anticancer assay was performed at approximatelysixty human tumor cell lines panel derived from nine neoplasticdiseases, in accordance with the protocol of the Drug Evaluation Branch, National Cancer Institute, Bethesda (
Using the absorbance measurements [time zero, (
[(
[(
spectrophotometrically versus controls not treated with the test agents.
Continuing our works (
Synthesis of 1
We investigated the reaction of 1
Synthesis of 5-(1
The structure of compounds
The synthesized compounds were selected by the National Cancer Institute (
The tested compounds displayed a weak to medium anticancer activity. The most sensitive cell lines turned out to be SNB-75 of CNS Cancer (GP = 74.84–85.73%) and UO-31, Renal cancer (GP = 71.53–82.16%) and to compound
Cytotoxic activity of the tested compounds in the concentration 10−5 M against 60 cancer cell lines.
Test compounds | Mitotic activity 60 cancer cell lines GP % | Most sensitive cell line (cancer line/type) GP, % | |
---|---|---|---|
Average growth, % | Range of growth, % | ||
|
98.93 | 74.37–143.90 | SNB-75 (CNS Cancer) 83.89 |
MALME-3M (Melanoma) 81.63 | |||
UO-31 (Renal Cancer) 74.37 | |||
|
100.30 | 76.42–122.20 | SNB-75 (CNS Cancer) 83.70 |
UO-31 (Renal Cancer) 76.42 | |||
|
100.49 | 78.88–127.16 | SNB-75 (CNS Cancer) 78.88 |
UO-31 (Renal Cancer) 80.50 | |||
|
101.36 | 73.79–154.33 | SNB-75 (CNS Cancer) 85.73 |
UO-31 (Renal Cancer) 73.79 | |||
|
101.23 | 81.40–136.54 | SNB-75 (CNS Cancer) 81.40 |
UO-31 (Renal Cancer) 82.16 | |||
|
101.06 | 71.53–127.99 | SNB-75 (CNS Cancer) 78.08 |
CAKI-1 (Renal Cancer) 83.37 | |||
UO-31 (Renal Cancer) 71.53 | |||
|
98.79 | 73.24–123.19 | SNB-75 (CNS Cancer) 75.43 |
UO-31 (CNS Cancer) 73.24 | |||
|
99.38 | 57.14–111.51 | K-562 (Leukemia) 57.14 |
SNB-75 (CNS Cancer) 74.84 | |||
UO-31 (Renal Cancer) 76.84 | |||
|
101.36 | 73.79–154.33 | SNB-75 (CNS Cancer) 85.73 |
UO-31 (Renal Cancer) 73.79 |
In our work, we presented an efficient synthesis and anticancer activity evaluation of some 5-(1