Acridine/Acridone–Carborane Conjugates as Strong DNA‐Binding Agents with Anticancer Potential

Abstract

Synthesis of acridine derivatives that act as DNA-targeting anticancer agents is an evolving field and has resulted in the introduction of several drugs into clinical trials. Carboranes can be of importance in designing biologically active compounds due to their specific properties. Therefore, a series of novel acridine analogs modified with carborane clusters were synthesized. The DNA-binding ability of these analogs was evaluated on calf thymus DNA (ct-DNA). Results of these analyses showed that 9-[(1,7-dicarba-closo-dodecaborane-1-yl)propylamino]acridine (30) interacted strongly with ct-DNA, indicating its ability to intercalate into DNA, whereas 9-[(1,7dicarba-closo-dodecaborane-1-yl)propanamido]acridine (29) changed the B-form of ct-DNA to the Z form. Compound 30 demonstrated cytotoxicity, was able to inhibit cell proliferation, arrest the cell cycle in the S phase in the HeLa cancer cell line, and induced the production of reactive oxygen species (ROS). In addition, it was specifically localized in lysosomes and was a weak inhibitor of Topo IIα.

Derivatives Incorporating Acridine, Pyrrole, and Thiazolidine Rings as Promising Antitumor Agents

“…Moreover, the precursor ions were systematically fragmented using distinct fragmentation techniques (CID and HCD) at various collision energies. These experiments resulted in a comprehensive collection of fragmentation spectra at each fragmentation level, spanning from MS 2 to MS 4 , allowing for the construction of a comprehensive spectral tree of information (Figures 11 and 12).…”

“…This property imparts cytotoxicity and anti-proliferative effects on cancer cells. Acridine derivatives have shown potential in inducing apoptosis [ 3 ], inhibiting tumor cell growth [ 4 ], and interfering with DNA repair mechanisms [ 5 , 6 ]. These compounds have demonstrated activity against a variety of cancers, including breast [ 7 ], lung [ 8 ], colon [ 9 ], and leukemia [ 10 ].…”

“…Oxo-1 -{[(2Z)-4-oxo-3-phenyl-1,3-thiazolidin-2-ylidene]amino}-1 ,5 -dihydro-10H-spiro[acridine-9,2 -pyrrole]-4 -carbonitrile (7a). Yellow solid; yield: 79% (0.043 g), m. p.: 241-243 • C (d).1 H NMR (600 MHz, DMSO-d 6 ): δ 9.77 (s, 1H, H-10 ), 8.69 (s, 1H, H-3), 7.29 (m, 3H, H-3 ,4 ,5 ), 7.26 (ddd, J = 8.4, 7.1, 1 4. Hz, 2H, H-3 ,6 ), 7.05 (m, 2H, H-2 ,6 ), 7.02 (dd, J = 8.2, 1.2 Hz, 2H, H-4 ,5 ), 7.02 (dd, J = 7.9, 1.4 Hz, 2H, H-1 ,8 ), 6.81 (ddd, J = 7.9, 7.1, 1.2 Hz, 2H, H-2 ,7 ), 4.03 (s, 2H, H-12) 13.…”

“…[(2Z,5Z)-2-({4 -cyano-5 -oxo-1 ,5 -dihydro-10H-spiro[acridine-9,2 -pyrrol]-1 -yl}imino)-4-oxo-3-phenyl-1,3-thiazolidin-5-ylidene]acetate (8a). Yellow solid; yield: 75% (0.048 g), m. p.: 256-259 • C (d).1 H NMR (600 MHz, DMSO-d 6 ): δ 9.80 (s, 1H, H-10 ), 8.77 (s, 1H, H-3), 7.33 (m, 3H, H-3 ,4 ,5 ), 7.25 (ddd, J = 8.2, 7.1, 1 4. Hz, 2H, H-3 ,6 ), 7.15 (m, 2H, H-2 ,6 ), 7.07 (dd, J = 7.9, 1 4.…”

“…Yellow solid; yield: 75% (0.048 g), m. p.: 256-259 • C (d).1 H NMR (600 MHz, DMSO-d 6 ): δ 9.80 (s, 1H, H-10 ), 8.77 (s, 1H, H-3), 7.33 (m, 3H, H-3 ,4 ,5 ), 7.25 (ddd, J = 8.2, 7.1, 1 4. Hz, 2H, H-3 ,6 ), 7.15 (m, 2H, H-2 ,6 ), 7.07 (dd, J = 7.9, 1 4. Hz, 2H, H-1 ,8 ), 7.01 (dd, J = 8.2, 1.2 Hz, 2H, H-4 ,5 ), 6.82 (ddd, J = 8.0, 7.1, 1.2 Hz, 2H, H-2 ,7 ), 6.73 (s, 1H, H-14), 4.25 (q, J = 7.1 Hz, 2H, H-16), 1.26 (t, J = 7.1 Hz, 3H, H-17) 13.…”