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Review
, 20 (6)

Hybrid cis-stilbene Molecules: Novel Anticancer Agents

Affiliations
Review

Hybrid cis-stilbene Molecules: Novel Anticancer Agents

Natalia Piekuś-Słomka et al. Int J Mol Sci.

Abstract

The growing interest in anticancer hybrids in the last few years has resulted in a great number of reports on hybrid design, synthesis and bioevaluation. Many novel multi-target-directed drug candidates were synthesized, and their biological activities were evaluated. For the design of anticancer hybrid compounds, the molecules of stilbenes, aromatic quinones, and heterocycles (benzimidazole, imidazole, pyrimidine, pyridine, pyrazole, quinoline, quinazoline) were applied. A distinct group of hybrids comprises the molecules built with natural compounds: Resveratrol, curcumin, coumarin, and oleanolic acid. In this review, we present the studies on bioactive hybrid molecules of a well-known tubulin polymerization inhibitor, combretastatin A-4 and its analogs with other pharmacologically active entities. The mechanism of anticancer activity of selected hybrids is discussed considering the structure-activity relationship.

Keywords: anticancer agents; hybrids; stilbenes.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of combretastatin A-4 (1) and its analogs in clinical trials (34).
Figure 2
Figure 2
The general structure of combretastatin based hybrids.
Figure 3
Figure 3
Chemical structures of piperlongumine (5) and its hybrids (6,7). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 4
Figure 4
Chemical structures of tamoxifen (8) and its hybrid (9). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 5
Figure 5
Chemical structures of chlorambucil (10) and its hybrid (11). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 6
Figure 6
Chemical structures of pironetin (12) and its hybrid (13-17). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 7
Figure 7
Chemical structures of 2(3H)benzoxazolone (18) and its hybrid (19). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 8
Figure 8
Chemical structures of benzothiazole (20) and its hybrids (21, 22). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 9
Figure 9
Chemical structures of cinnamic acid (23) and its hybrids (24,25). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 10
Figure 10
Chemical structures of isocombretastatin (26) and its hybrid (27). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 11
Figure 11
Chemical structures of 2-azetidione/β-lactam (28) and its hybrid (29). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 12
Figure 12
Chemical structures of 2,3-dihydroquinazolinone (30), isoxazoline (31), isoxazole (32) and their hybrid (33). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 13
Figure 13
Chemical structures of lamellarins (34, 37) and their hybrids (35, 36, 38). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 13
Figure 13
Chemical structures of lamellarins (34, 37) and their hybrids (35, 36, 38). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 14
Figure 14
Chemical structures of oltipraz (39) and its hybrids (40-43). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 15
Figure 15
Chemical structures of chromone (44) and its hybrid (45). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 16
Figure 16
Chemical structures of phenstatin (46) and its hybrids (47, 48). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 17
Figure 17
Chemical structures of chalcone (47) and its hybrids (50–57). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 18
Figure 18
Chemical structures of estradiol (58) and its hybrids (59, 60). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 19
Figure 19
Chemical structures of isatin (61) and its hybrid (62). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 20
Figure 20
Chemical structures of quinoline (63) and its hybrids (6469). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 21
Figure 21
The chemical structure of combretatropone (70).
Figure 22
Figure 22
Chemical structures of nocodazole (71) and its hybrids (72-74). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 23
Figure 23
Biological activities of cis-stilbene hybrids.
Figure 24
Figure 24
Chemical structures of cisplatin (75) and its hybrid (76). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 25
Figure 25
Chemical structures of belinostat (77), it’s hybrids (78, 79, 80). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 25
Figure 25
Chemical structures of belinostat (77), it’s hybrids (78, 79, 80). Entity I (cis-stilbene) and entity II were depicted with the blue (· · · · · · ·), and red (– – – –) dotted lines, respectively.
Figure 26
Figure 26
Chemical structures of rofecoxib (81), celecoxib (82) and their hybrids (83, 84).

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