- Design, synthesis, and molecular docking of novel indole scaffold-based VEGFR-2 inhibitors as targeted anticancer agents
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A series of new indole derivatives 1–18 was synthesized and tested for their cytotoxic activity on a panel of 60 tumor cell lines. Additionally, molecular docking was carried out to study their binding pattern and binding affinity in the VEGFR-2 active site using sorafenib as a reference VEGFR-2 inhibitor. Based on the molecular docking results, compounds 5a, 5b, 6, 7, 14b, 18b, and 18c were selected to be evaluated for their VEGFR-2 inhibitory activity. Compound 18b exhibited a broad-spectrum antiproliferative activity on 47 cell lines, with GI % ranging from 31 to 82.5%. Moreover, compound 18b was the most potent VEGFR-2 inhibitor with an IC50 value of 0.07 μM, which is more potent than that of sorafenib (0.09 μM). A molecular docking study attributed the promising activity of this series to their hydrophobic interaction with the VEGFR-2 binding site hydrophobic side chains and their hydrogen bonding interaction with the key amino acids Glu885 and/or Asp1046.
- Roaiah, Hanaa M.,Ghannam, Iman A. Y.,Ali, Islam H.,El Kerdawy, Ahmed M.,Ali, Mamdouh M.,Abbas, Safinaz E-S.,El-Nakkady, Sally S.
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- Inhibition studies on a panel of human carbonic anhydrases with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails
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Being the primary sulfonamide among the most efficient zinc binding group (ZBG) to design inhibitors for the metallo-enzymes carbonic anhydrases (CA, EC 4.2.1.1), herein, we propose an investigation on four physiologically important human (h) CAs (hCA I, II, IV, and IX) with N1-substituted secondary sulfonamides incorporating thiazolinone or imidazolone-indole tails. The effect of the functionalisation of the sulfonamide group with five different substitution patterns, namely acetyl, pyridine, thiazole, pyrimidine, and carbamimidoyl, was evaluated in relation to the inhibition profile of the corresponding primary sulfonamide analogues. With most of these latter being nanomolar inhibitors of all four considered isoforms, a totally counterproductive effect on the inhibition potency can be ascribed to N1-functionalisations of the ZBG primary sulfonamide structure with pyridine, thiazole, and pyrimidine moieties. On the other hand, incorporation of less hindered groups, such as sulfonylacetamides and sulfonylguanidines, maintained a certain degree of activity dependent on the tailing moiety, with KIs spanning in the low micromolar range.
- Awadallah, Fadi M.,Bua, Silvia,Mahmoud, Walaa R.,Nada, Hossam H.,Nocentini, Alessio,Supuran, Claudiu T.
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p. 629 - 638
(2018/03/26)
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- Design, synthesis and biological evaluation of some novel chalcones-sulphonamide hybrids
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A new class of Chalcone-Sulphonamide hybrids has been designed by condensing appropriate sulphonamide scaffold with substituted chalcones tethered by chloroacetyl chloride as a multi-target drug for therapeutic treatment. Chalcones were prepared by Claisen-Schmidt condensation of a substituted aldehyde with para aminoacetophenone. These Chalcone-Sulphonamide hybrids were screened by means of their antibacterial activity by NCCLS method. Among all these compounds, 5e and 5c displayed more potent growth inhibitory activity against Staphylococcus epidermidis and Pseudomonas aeruginosa bacteria respectively. Further, these hybrids were evaluated for their antifungal activity, among all hybrid 5a exhibited potent antifungal activity. The synthesized compounds were characterized by FT-IR, 1HNMR, 13CNMR and HR-LCMS and spectral study supports the structures of synthesized Chalcone-Sulphonamide hybrids.
- Khanusiya, Mahammadali,Gadhawala, Zakirhusen
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p. 377 - 385
(2018/10/15)
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- New antimicrobial chitosan derivatives for wound dressing applications
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Chitosan is a non-toxic, biocompatible, biodegradable natural cationic polymer known for its low imunogenicity, antimicrobial, antioxidant effects and wound-healing activity. To improve its therapeutic potential, new chitosan-sulfonamide derivatives have
- Dragostin, Oana Maria,Samal, Sangram Keshari,Dash, Mamoni,Lupascu, Florentina,Panzariu, Andreea,Tuchilus, Cristina,Ghetu, Nicolae,Danciu, Mihai,Dubruel, Peter,Pieptu, Dragos,Vasile, Cornelia,Tatia, Rodica,Profire, Lenuta
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- Synthesis, carbonic anhydrase inhibition and cytotoxic activity of novel chromone-based sulfonamide derivatives
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Four series of sulfonamides incorporating chromone moieties were synthesized and assessed for their cytotoxic activity against MCF-7 and A-549 cell lines, considering the fact that some of these tumors overexpress isoforms of carbonic anhydrase (CA, EC 4.2.1.1) which is inhibited by sulfonamides. Most new sulfonamides showed weak inhibitory activity against the offtarget, cytosolic isoforms hCA I, II but effectively inhibited the tumor-associated hCA IX and XII. The most active compounds featured a primary SO2NH2 group and were active in the low micromolar range against MCF-7 and A-549 cell lines. Compound 4a showed IC50 of 0.72 and 0.50 1/4M against MCF-7 and A-549 cell lines, respectively, and was further evaluated for its proapoptotic activity which proved enhanced in both tumor types.
- Awadallah, Fadi M.,El-Waei, Tamer A.,Hanna, Mona M.,Abbas, Safinaz E.,Ceruso, Mariangela,Oz, Beyza Ecem,Guler, Ozen Ozensoy,Supuran, Claudiu T.
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p. 425 - 435
(2015/05/05)
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- Improvement of antibacterial activity of some sulfa drugs through linkage to certain phthalazin-1(2H)-one scaffolds
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RAB1 5 is a lead antibacterial agent in which trimethoprim is linked to phthalazine moiety. Similarly, our strategy in this research depends on the interconnection between some sulfa drugs and certain phthalazin-1(2H)-one scaffolds in an attempt to enhance their antibacterial activity. This approach was achieved through the combination of 4-substituted phthalazin-1(2H)-ones 9a, b or 14a, b with sulfanilamide 1a, sulfathiazole 1b or sulfadiazine 1c through amide linkers 6a, b to produce the target compounds 10a-d and 15a-e, respectively. The antibacterial activity of the newly synthesized compounds showed that all tested compounds have antibacterial activity higher than that of their reference sulfa drugs 1a-c. Compound 10c represented the highest antibacterial activity against Gram-positive bacteria Streptococcus pneumonia and Staphylococcus aureus with MIC = 0.39 μmol/mL. Moreover, compound 10d displayed excellent antibacterial activity against Gram-negative bacteria Escherichia coli and Salmonella typhimurium with MIC = 0.39 and 0.78 μmol/mL, respectively.
- Ibrahim, Hany S.,Eldehna, Wagdy M.,Abdel-Aziz, Hatem A.,Elaasser, Mahmoud M.,Abdel-Aziz, Marwa M.
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p. 480 - 486
(2014/09/03)
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- Synthesis and biological evaluation of new 2-azetidinones with sulfonamide structures
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New series of N-(arylidene)hydrazinoacetyl sulfonamides 4a1-6, 4b1-6 and N-(4-aryl-3-chloro-2-oxoazetidin-1-yl)aminoacetyl sulfonamides 5a1-6, 5b1-6 were synthesized. The structures of the new derivatives was co
- Dragostin, Oana Maria,Lupascu, Florentina,Vasile, Cornelia,Mares, Mihai,Nastasa, Valentin,Moraru, Ramona Florina,Pieptu, Dragos,Profire, Lenuta
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p. 4140 - 4157
(2013/05/22)
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- Synthesis of new 2-(substituted benzothiazolylcarbamoyl)benzimidazoles as potential CNS depressants
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The synthesis of a series of 2-(substituted benzothiazolylcarbamoyl/benzothiazolylamino-carbamoyl)benzimidazoles 41-60 is reported. Their synthesis has been achieved by chloroacetylating the substituted 2-aminobenzothiazoles and 2-hydrazinobenzothiazoles. The N- chloroacetyl derivatives thus formed have been reacted with o- phenylenediamine in the presence of sulphur to afford the final products. Extension of this sequence of reaction by incorporating certain sulphonamidohydrazines is also described.
- Sharma, Pratibha,Mandloi, Anupam,Pritmani, Shreeya
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p. 1289 - 1294
(2007/10/03)
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