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1.
Sci Rep ; 14(1): 13028, 2024 06 06.
Article in English | MEDLINE | ID: mdl-38844493

ABSTRACT

New sulfonamide-triazole-glycoside hybrids derivatives were designed, synthesised, and investigated for anticancer efficacy. The target glycosides' cytotoxic activity was studied with a panel of human cancer cell lines. Sulfonamide-based derivatives, 4, 7 and 9 exhibited promising activity against HepG-2 and MCF-7 (IC50 = 8.39-16.90 µM against HepG-2 and 19.57-21.15 µM against MCF-7) comparing with doxorubicin (IC50 = 13.76 ± 0.45, 17.44 ± 0.46 µM against HepG-2 and MCF-7, rescpectively). To detect the probable action mechanism, the inhibitory activity of these targets was studied against VEGFR-2, carbonic anhydrase isoforms hCA IX and hCA XII. Compoumds 7 and 9 gave favorable potency (IC50 = 1.33, 0.38 µM against VEGFR-2, 66, 40 nM against hCA IX and 7.6, 3.2 nM against hCA XII, respectively), comparing with sorafenib and SLC-0111 (IC50 = 0.43 µM, 53 and 4.8 nM, respectively). Moreover, the docking simulation was assessed to supply better rationalization and gain insight into the binding affinity between the promising derivatives and their targeted enzymes that was used for further modification in the anticancer field.


Subject(s)
Antineoplastic Agents , Carbonic Anhydrase Inhibitors , Glycosides , Molecular Docking Simulation , Sulfonamides , Triazoles , Vascular Endothelial Growth Factor Receptor-2 , Humans , Carbonic Anhydrase Inhibitors/chemistry , Carbonic Anhydrase Inhibitors/pharmacology , Sulfonamides/chemistry , Sulfonamides/pharmacology , Glycosides/chemistry , Glycosides/pharmacology , Triazoles/chemistry , Triazoles/pharmacology , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-2/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Carbonic Anhydrase IX/metabolism , Carbonic Anhydrase IX/antagonists & inhibitors , Carbonic Anhydrases/metabolism , Carbonic Anhydrases/chemistry , MCF-7 Cells , Hep G2 Cells , Cell Line, Tumor , Antigens, Neoplasm/metabolism , Structure-Activity Relationship
2.
Molecules ; 27(20)2022 Oct 17.
Article in English | MEDLINE | ID: mdl-36296551

ABSTRACT

New 1,3,4-thiadiazole thioglycosides linked to a substituted arylidine system were synthesized via heterocyclization via click 1,3-dipolar cycloaddition. The click strategy was used for the synthesis of new 1,3,4-thiadiazole and 1,2,3-triazole hybrid glycoside-based indolyl systems as novel hybrid molecules by reacting azide derivatives with the corresponding acetylated glycosyl terminal acetylenes. The cytotoxic activities of the compounds were studied against HCT-116 (human colorectal carcinoma) and MCF-7 (human breast adenocarcinoma) cell lines using the MTT assay. The results showed that the key thiadiazolethione compounds, the triazole glycosides linked to p-methoxyarylidine derivatives and the free hydroxyl glycoside had potent activity comparable to the reference drug, doxorubicin, against MCF-7 human cancer cells. Docking simulation studies were performed to check the binding patterns of the synthesized compounds. Enzyme inhibition assay studies were also conducted for the epidermal growth factor receptor (EGFR), and the results explained the activity of a number of derivatives.


Subject(s)
Antineoplastic Agents , Thioglycosides , Humans , Molecular Docking Simulation , Triazoles/chemistry , Glycosides/pharmacology , Azides/pharmacology , Structure-Activity Relationship , Cell Proliferation , Thioglycosides/chemistry , Antineoplastic Agents/chemistry , ErbB Receptors/metabolism , MCF-7 Cells , Doxorubicin/pharmacology , Alkynes/pharmacology , Molecular Structure , Drug Screening Assays, Antitumor
3.
Anticancer Agents Med Chem ; 21(10): 1323-1333, 2021.
Article in English | MEDLINE | ID: mdl-32990545

ABSTRACT

BACKGROUND & OBJECTIVE: Glycosyl heterocycles, being as nucleoside analogs with modified glycon and hybrid heterocycle motifs, are of considerable interest, and thus, the targeted compounds were synthesized via a convenient and efficient approach. METHODS: New indolyl-thiadiazolyl thioglycosides scaffolds were synthesized, starting with the reaction of indole-3-carbaldehyde with 2-aminothiadiazole-5-thiole followed by glycosylation and deprotection. Likewise, new molecular hybrids comprising indole, thiadiazole, triazole and glycosyl moieties were synthesized utilizing click chemistry strategy. The cytotoxic activities of the newly synthesized compounds were studied on colon carcinoma HCT116, breast carcinoma MCF-7, lung carcinoma A549 and hepatocellular carcinoma HepG2 cell lines using Sulphorhodamine-B (SRB) assay. RESULTS: The 1,3,4-thiadiazole thioglycoside and the 1,2,3-triazole N1-glycoside possessing xylose moiety, compounds 8 and 15 revealed the most potent bio-activity among the new chemical entities; therefore, they undertook for further analysis of apoptosis. CONCLUSION: IC50s of Compound 8 were 38, 36, 33 and 158µg/ml, while they were 41, 44, 32 and 25µg/ml for compound 15 on HepG2, MCF7, HCT116 and A549 cell lines, respectively; furthermore, the total apoptosis rate (%) for control untreated cells were 9.63, 28.4, 25.4 (%), compounds 8 and 15 respectively, they produced a significant increase in total and early apoptosis rate (%) compared to control (P=0.0001). At the same time, no significant difference was detected in the late apoptosis rate (%), which means that both derivatives have the potential to be developed into potent anticancer agents.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Glycosides/pharmacology , Indoles/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Glycosides/chemistry , Humans , Indoles/chemistry , Molecular Structure , Structure-Activity Relationship
4.
Molecules ; 24(20)2019 Oct 16.
Article in English | MEDLINE | ID: mdl-31623291

ABSTRACT

New 1,3,4-thiadiazole thioglycosides linked to substituted arylidine systems were synthesized via glycosylation of the prepared 1,3,4-thiadiazole thiol compounds. Click strategy was also used for the synthesis of new 1,3,4-thiadiazole and 1,2,3-triazole hybrid glycosides by reaction of the acetylenic derivatives with different glycosyl azids followed by deacetylation process. The cytotoxic activities of the prepared compounds were studied against HCT-116 (human colorectal carcinoma) and MCF-7 (human breast adenocarcinoma) cell lines using the MTT assay. The results showed that the key thiadiazolethione compounds 2 and 3, the triazole glycosides linked to p-methoxyarylidine derivatives 14 and 15 in addition to the free hydroxyl glycoside 20 were found potent in activity comparable to the reference drug doxorubicin against MCF-7 human cancer cells. The acetylenic derivative 2 and glycoside 20 were also found highly active against HCT-116 cell lines.


Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Thiadiazoles/chemistry , Thioglycosides/chemical synthesis , Thioglycosides/pharmacology , Triazoles/chemistry , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Humans , Molecular Structure , Structure-Activity Relationship , Thioglycosides/chemistry
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