10.1016/j.ejmech.2010.03.026
The research focused on the synthesis and evaluation of antitumor activity of thiosemicarbazones derived from the natural sesquiterpene (±)-α-bisabolol against a panel of eight human tumor cell lines. The purpose was to assess their potential as anti-cancer agents and to identify structure-activity relationships that contribute to their antitumor activity. The study concluded that some of the synthesized compounds, particularly the ketone derivative 3l, exhibited potent antitumor activity and high selectivity for myeloid leukemia cells (K-562), with compound 3l showing superior activity compared to the standard drug doxorubicin. The chemicals used in the process included (±)-α-bisabolol, isothiocyanate, hydrazine, and various benzaldehyde derivatives, as well as acetophenone or benzophenone, with catalytic amounts of sulfuric acid used in the reaction. The synthesized thiosemicarbazones were then tested for their inhibitory effects on cancer cell growth, leading to the identification of structural requirements for enhanced antitumor activity.
10.1002/jhet.749
The study investigates the synthesis and evaluation of novel quinoline derivatives for their anticancer and radiosensitizing properties. The researchers synthesized a series of quinoline derivatives (6–12) and pyrimido[4,5-b]quinoline derivatives (16–20) to assess their potential as inhibitors of vascular endothelial growth factor receptor tyrosine kinase (VEGFR-TK), which is implicated in cancer cell proliferation and angiogenesis. The compounds were evaluated for their in vitro anticancer activity against the human breast cancer cell line MCF7, which overexpresses VEGFR. Notably, compounds 6 and 7 exhibited significant cytotoxic activity, with IC50 values of 8.5 μM and 21.9 μM, respectively, surpassing the reference drug doxorubicin (IC50 = 32.02 μM). These two compounds were further tested for their ability to enhance the cell-killing effect of gamma radiation, showing a synergistic decrease in IC50 values when combined with radiation. The study also utilized molecular modeling to generate a pharmacophore hypothesis for VEGFR-TK inhibitors and conducted docking studies to explore the binding modes of the synthesized compounds, revealing that compound 7 had a binding mode similar to the known VEGFR-TK inhibitor Vatalanib. The results suggest that some of the synthesized compounds may act as VEGFR-TK inhibitors, contributing to their anticancer activity and radiosensitizing effects.
10.1016/j.bmc.2008.08.076
The study focuses on the design, synthesis, and evaluation of D-galactose-?-cyclodextrin (D-gal-?-CyD) conjugates as drug-carrying molecules. The researchers synthesized several types of D-gal-?-CyD conjugates (4–7) with phenyl groups in the spacers between D-galactose and ?-CyD. These conjugates were designed to have high inclusion associations with the anticancer drug doxorubicin (DXR) and strong binding affinities with peanut lectin (PNA), a D-galactose-binding protein. The conjugates were evaluated using surface plasmon resonance (SPR) optical biosensor techniques to measure their interactions with immobilized DXR and PNA. The results showed that the conjugates had high inclusion associations of 105–107 M–1 levels for DXR and association constants of 104–105 M–1 levels for PNA, indicating their potential as effective drug-carrying molecules for targeted drug delivery systems. The study also demonstrated in situ dual molecular interactions of one of the conjugates (4) with both DXR and PNA using SPR, further confirming the feasibility of these conjugates for selective drug delivery to cells containing D-galactose-binding lectin.
10.1016/j.ejmech.2011.08.026
The research aimed to synthesize and evaluate the anticancer and radiosensitizing properties of novel thiazolo[4,5-b]pyrane and thiazolo[4,5-b]pyrano[2,3-d]pyrimidine derivatives containing a sulfonamide group. The study was motivated by the known anticancer activities of sulfonamide compounds, particularly through the inhibition of carbonic anhydrase isozymes. Key chemicals used included 4-(4-oxo-4,5-dihydrothiazol-2ylamino)benzenesulfonamide (3) as a starting material, and various reagents such as 2-(4-chlorobenzylidene)malononitrile, formic acid, acetic anhydride, and aromatic aldehydes to synthesize the target compounds. The newly synthesized compounds were tested for their in vitro anticancer activity against the human breast cancer cell line (MCF7), with several showing significant cytotoxic activity compared to the reference drug doxorubicin. Notably, compounds 5, 6, 10, and 12 exhibited higher cytotoxic activities than doxorubicin. Doxorubicin is used as a reference drug to compare the anticancer activity of the newly synthesized thiazolopyrane and thiazolopyranopyrimidine derivatives. Doxorubicin is a well-known and widely used anticancer agent, particularly effective against various types of cancer, including breast cancer. These compounds were further evaluated for their ability to enhance the cell-killing effect of gamma radiation, with compound 12 showing a synergistic decrease in IC50 value when combined with radiation. The study concluded that these new compounds not only possess significant anticancer activity but also have the potential to sensitize cancer cells to ionizing radiation, suggesting their potential use in combination therapies for cancer treatment.
10.1021/jm00157a027
The research aimed to synthesize and evaluate the antitumor properties of the 9-aza analogue of N-(trifluoroacetyl)-4-demethoxydaunomycin, a derivative of the anthracycline antibiotics doxorubicin and daunomycin. The study hypothesized that the bioisosteric replacement of carbon with nitrogen in the alicyclic A ring of the glycosides could potentially enhance antitumor activity. The synthesis involved a series of chemical reactions, including Pomeranz-Fritsch condensation, borohydride reduction, acid-catalyzed cyclization, selective N-acetylation, Friedel-Crafts acylation, epoxidation, and glycosidation with N,O-bis(trifluoroacetyl)daunosamine bromide and silver trifluoromethanesulfonate. The resulting diastereoisomers were separated and their structures confirmed using CD and NMR spectroscopy. However, the study concluded that both diastereoisomers were inactive in mice carrying the P388 tumor, suggesting that the side-chain keto moiety could not be replaced by an aliphatic amide group without losing antitumor activity. The chemicals used in the process included 2,5-dimethoxy-benzaldehyde, 2-aminoacetaldehyde dimethyl acetal, sodium borohydride, phthalic anhydride, and various reagents for protection and deprotection of functional groups, as well as for the final glycosidation step.
10.1021/jm0612158
The study investigates the development of a new series of spirodiketopiperazine derivatives for their cytotoxic potential against various human tumor cell lines. The researchers synthesized these compounds by condensing the 3-amino-3(ethoxycarbonyl)-2,3-dihydrothieno[2,3-b]naphtho-4,9-dione system with various amino acids, followed by intramolecular lactamization. The study evaluated the cytotoxic activity of these derivatives against MCF-7 human breast carcinoma and SW 620 human colon carcinoma cell lines, revealing that certain isomers derived from Proline (Pro), Cysteine (Cys), and Methionine (Met) exhibited cytotoxic potency comparable to or greater than that of doxorubicin. The study also explored the topoisomerase II inhibition activity and DNA-binding properties of these compounds. The results suggest that these derivatives could potentially circumvent multiple-drug resistance mechanisms and have significant cytotoxic effects on various tumor cell lines, including those resistant to doxorubicin and cisplatin.
10.1021/jm00157a025
The study investigates the preparation and biological evaluation of thio ester analogues of the antitumor antibiotic adriamycin and its derivative N-(trifluoroacetyl)adriamycin. The researchers synthesized a series of N-(trifluoroacetyl)adriamycin 14-thio esters (compounds 3a-e) and adriamycin 14-thio esters (compounds 4a-e) using reactions with various thio acids and N-(trifluoroacetyl)-14-bromodaunorubicin or 14-bromodaunorubicin, respectively. These compounds were evaluated for their in vitro growth-inhibitory activity against human leukemic cells, in vivo antitumor activity in a murine P388 leukemia model, and the rate of thio ester deacylation by esterases in mouse serum. The study found that while the adriamycin thio esters (4a-e) exhibited significant in vivo antitumor activity and interacted with DNA similarly to adriamycin, none of the N-(trifluoroacetyl)adriamycin thio esters (3a-e) showed biological activity. The results suggest that the presence of a sulfur function in the thio ester structure significantly affects the biological activity and metabolic stability of these compounds.
