Synthesis, Anti-Breast Cancer and Molecular Docking of Some Heterocycles Incorporating N,N-Dibenzylbenzenesulfonamide
Abstract: Reaction of 1 with dimethylformamide-dimethylacetal (DMF-DMA) gave enaminone 2, which reacts with p-toluidine and phenylhydrazine to afford 3 and 5, respectively. Treatment of 2 with 1,4-benzoquinone gave 5-hydroxybenzofuran derivative 9. Hydrazonyl bromide 10 reacts with 2 in refluxing xylene-TEA to give ethyl pyrazole-3-carboxylate derivative 15, which on treatment with ethanolic hydrazine hydrate gave pyrazolo[3,4-d]pyridazine derivative 16. Enaminone 2 reacts with heterocyclic amines to furnished new heterocyclic systems, pyrazolo[1,5-a]pyrimidine 22, triazolo[4,3-a]pyrimidine 28 and pyrimido[1,6-a]pyrimidine 34. Also, enaminone 2 reacts with guanidine.HCl, hydrazine hydrate, p-chlorobenzenediazonium chloride and hydroxylamine.HCl to afford the corresponding derivatives of 2-aminopyrimidine 35, pyrazole 36, 2-arylhydrazonopropanal 37 and cyanoacetyl 46, respectively. Enaminone 2 reacts with phenylisothiocyanate in DMF-KOH through nucleophilic addition of enaminone C-2 to give 47. Interaction of 2 with active methylene compounds afforded cyanopyridine 53 and imidazo[1,2-a]pyridine 56, derivatives. On the other hand enaminone 2 reacts with ethylenediamine and alanine to afford derivatives of diazepine 58 and oxazepine 60, respectively. Reaction of 2 with dimethyl acetylenedicarboxylate and acetyl acetone afforded derivatives of pyranone 64 and pyridine 66, respectively. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H-NMR, 13C-NMR and Ms spectral data. All the newly synthesized compounds were tested in-vitro anti-breast cancer cell line (MCF7). Compounds 56, 53, 36, 15, 46, 37, 9, 16, 64, 28, 35 and 2 with IC50 values (170.3, 157.5, 153.1, 146.9, 143.2, 140.0, 127.9, 122.7, 121.3, 119.5, 117.3, 111.9, ?M), respectively, exhibited better activity than methotrexate as a reference drug with IC50 value (74.6 ?M). Virtual screening using molecular docking studies of the synthesized compounds was performed by (MOE), the molecular docking results indicate that, some synthesized compounds suitable inhibitor against dihydrofolate reductase (DHFR) enzyme (PDB ID: 4DFR) with further modification.
[MAHMOUD SAYED BASHANDY (2014); Synthesis, Anti-Breast Cancer and Molecular Docking of Some Heterocycles Incorporating N,N-Dibenzylbenzenesulfonamide Int. J. of Adv. Res. 2 (10). 0] (ISSN 2320-5407). www.journalijar.com
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