Abstract
This article describes the synthesis of some novel sulfonamides having the biologically active, thi-azole 4-6, 8, 10-12a,b, 20, 22, 34, 35, imidazo[1,2-a]pyridine 14, imidazo[2,1-c][1,2,4]triazole 15, imidazo[2,1-b]thiazole 23, 24, 33, nicotinonitrile 25, 1,3,4-thiadiazine 27, quinoxaline 30 and 1,4-thiazine 31 moieties, starting with 1-(4-(pyrrolidin-1-ylsulfonyl)phenyl)ethanone (1). The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR, 13C NMR and Ms spectral data. All the compounds were tested in-vitro antihuman liver hepatocellular carcinoma cell line (HepG2). Compounds 8, 11, 4, 22, 12a, 33, 35, 27 and 24 with selectivity index (SI) values of 33.21, 30.49, 19.43, 14.82, 10.29, 7.3, 6.87, 6.15 and 4.62, respectively, exhibited better activity than methotrexate (MTX) as a reference drug with SI value of 4.14. Molecular Operating Environment (MOE) performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some synthesized compounds are suitable inhibitors against dihydrofolate reductase (DHFR) enzyme (PDB ID: 4DFR) with further modification.
Highlights
Sulfonamides have been demonstrated to possess antibacterial [1]-[3], antifungal [4], insulin-releasing [5] [6], carbonic anhydrase inhibitory [7]-[9], hypoglycemic [10], anesthetic [11], anti-inflammatory [12] [13], andanticarcinogenic [14] [15] activities
Liver cancer remains one of the most important health problems in the world because it is the third foremost cause of cancer-related deaths worldwide [16]. In view of these reports and as a continuation of previous works [17]-[21] directed towards the synthesis of substituted heterocycles, incorporating benzenesulfonamide with anticipated biological activities, this article reports new and convenient methods for the synthesis of heterocyclic ring systems that are required to medicinal chemistry utilizing 1-(4-(pyrrolidin-1-ylsulfonyl)phenyl)ethanone (1) as a starting material
Analyses were carried out by the Micro analytical Research Center, Faculty of Science, Cairo University and Al-Azhar University. 1-(4-(Pyrrolidin-1-ylsulfonyl)phenyl)ethanone (1) was prepared according to the procedures reported in the literature [22]
Summary
Sulfonamides have been demonstrated to possess antibacterial [1]-[3], antifungal [4], insulin-releasing [5] [6], carbonic anhydrase inhibitory [7]-[9], hypoglycemic [10], anesthetic [11], anti-inflammatory [12] [13], andanticarcinogenic [14] [15] activities. Liver cancer (hepatocellular carcinoma) remains one of the most important health problems in the world because it is the third foremost cause of cancer-related deaths worldwide [16] In view of these reports and as a continuation of previous works [17]-[21] directed towards the synthesis of substituted heterocycles, incorporating benzenesulfonamide with anticipated biological activities, this article reports new and convenient methods for the synthesis of heterocyclic ring systems that are required to medicinal chemistry utilizing 1-(4-(pyrrolidin-1-ylsulfonyl)phenyl)ethanone (1) as a starting material. The carbonyl and the methyl functions of compound 1 suitably situated to enable reaction with common bi-dentate reagents to form a variety of heterocyclic compounds having sulfonamide function, and investigated their anti- human liver cancer activities
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
