Study of reactivity of cyanoacetohydrazonoethyl-N-ethyl-N-methyl benzenesulfonamide: preparation of novel anticancer and antimicrobial active heterocyclic benzenesulfonamide derivatives and their molecular docking against dihydrofolate reductase.

This article describes the synthesis of some novel heterocyclic sulfonamides having biologically active thiophene 3, 4, 5, 6, coumarin 8, benzocoumarin 9, thiazole 7, piperidine 10, pyrrolidine 11, pyrazole 14 and pyridine 12, 13. Starting with 4-(1-(2-(2-cyanoacetyl)hydrazono)ethyl)-N-ethyl-N-methylbenzenesulfonamide (2), which was prepared from condensation of acetophenone derivative 1 with 2-cyanoacetohydrazide. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR, 13C NMR, 19F NMR and MS spectral data. All the newly synthesized heterocyclic sulfonamides were evaluated as in-vitro anti-breast cancer cell line (MCF7) and as in-vitro antimicrobial agents. Compounds 8, 5 and 11 were more active than MTX reference drug and compounds 12, 7, 4, 14, 5 and 8 were highly potent against Klebsiella pneumonia. Molecular operating environment performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some prepared compounds are suitable inhibitor against dihydrofolate reductase (DHFR) enzyme (PDBSD:4DFR) with further modification.

Design, synthesis and molecular docking of novel N,N-dimethylbenzenesulfonamide derivatives as potential antiproliferative agents.

Novel pyridine, thiophene, thiazole, chromene and benzochromene derivatives bearing a N,N-dimethylbenzenesulfonamide moiety 6-20 were synthesized. The target compounds were obtained through employing a series of heterocyclization reactions utilizing the key intermediate hydrazide hydrazone derivative 3. The structures of the newly synthesized compounds were confirmed by elemental analyses, IR, (1)H-NMR and (13)C-NMR spectral data. All the newly synthesized compounds were evaluated for their in vitro antiproliferative activity against the human breast cancer cell line MCF-7. Biological screening results showed that sulfonamides 6, 9, 11, 16 and 17 with IC50 values 21.81, 25.50, 20.60, 25.83 and 31.20 µM, respectively, possessed higher antiproliferative activity compared to doxorubicin, IC50 value 32.00 µM, as position control. Molecular docking study was also performed to assess the binding mode of the synthesized sulfonamides with their potential biomolecular target, carbonic anhydrase IX (CA IX), which is usually highly expressed in some types of cancer cells.

Synthesis, spectroscopic properties, molecular docking, anti-colon cancer and anti-microbial studies of some novel metal complexes for 2-amino-4-phenylthiazole derivative.

This article describes the synthesis of novel bidentate Schiff base (H2L) from condensation of 2-amino-4-phenylthiazole (APT) with 4,6-diacetylresorcinol (DAR) in the molar ratio 2:1. We studied interaction of ligand (H2L) with transition metal ions such as Cr(III), Fe(III), Cu(II), Zn(II) and Cd(II). The ligand (H2L) has two bidentate sets of (N-O) units which can coordinate with two metal ions to afford novel binuclear metal complexes. The directions of coordinate bonds are from nitrogen atoms of azomethine groups and oxygen atoms of the phenolic groups. Structures of the newly synthesized complexes were confirmed by elemental analysis, IR, UV, (1)H NMR, ESR, TGA and mass spectral data. All of the newly synthesized complexes were evaluated for their antibacterial and anti-fungal activities. They were also evaluated for their in vitro anticancer activity against human colon carcinoma cells (HCT-116) and mammalian cells of African green monkey kidney (VERO). The Cu(II) complex with selectivity index (S.I.)=21.26 exhibited better activity than methotrexate (MTX) as a reference drug with S.I. value=13.30, while Zn(II) complex with S.I. value=10.24 was found to be nearly as active as MTX. Molecular docking studies further helped in understanding the mode of action of the compounds through their various interactions with active sites of dihydrofolate reductase (DHFR) enzyme. The observed activity of Fe(III) and Cu(II) complexes gave rise to the conclusion that they might exert their action through inhibition of the DHFR enzyme.

Novel thiophene derivatives with sulfonamide, isoxazole, benzothiazole, quinoline and anthracene moieties as potential anticancer agents.

A novel series of thiophenes having biologically active sulfonamide 2-11, 3-methylisoxazole 12, 4-methoxybenzo[d] thiazole 13, quinoline 14, 15, benzoylphenylamino 16, and anthracene-9,10-dione 17 moieties were prepared. Structures of the newly synthesized compounds were established by elemental analysis and spectral data. All newly synthesized compounds were evaluated for their in vitro anticancer activity against human breast cancer cell line (MCF7). Most of the screened compounds showed cytotoxic activities compared to doxorubicin as a positive control. Compounds 6, 7, 9 and 13 (IC50 values 10.25, 9.70, 9.55 and 9.39 µmol L-1) revealed higher cytotoxic activities than that of doxorubicin (IC50 = 32.00 µmol L-1). Also, compounds 5, 8 and 10 were found nearly as active as doxorubicin (IC50 28.85, 23.48 and 27.51 µmol L-1).

Novel quinolines bearing a biologically active trimethoxyphenyl moiety as a new class of antitumor agents.

The present paper describes the synthesis of some novel 2-amino-4-substituted aryl-5-oxo-1-(3,4,5-trimethoxy)-1,4,5,6,7,8-hexahydroquinoline-3-carbo-nitriles 6a-s starting with 3-(3,4,5-trimethoxyanilino)cyclohex-2-enone 3. All the newly synthesized compounds were evaluated for their in vitro antitumor activity. Compounds 6j, 6p and 6 q showed higher activity with IC50 values 10, 10, 15 microg/mL, respectively, when compared with doxorubicin as a reference drug (IC50 value 37.5 microg/mL).

Anti-breast cancer activity of some novel 1,2-dihydropyridine, thiophene and thiazole derivatives.

A variety of novel 1,2-dihydropyridines 10-17, thiophenes 18-21 and thiazole 22 having a biologically active sulfone moiety were obtained via the reaction of 2-cyano-N'-[1-(4-(piperidin-1-ylsulfonyl) phenyl) ethylidene] acetohydrazide 3 with a variety of reagents. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in-vitro anticancer activity against human breast cancer cell line (MCF7). Compounds 15 and 11 with IC(50) values (20.6, 25.5 µM) exhibited better activity than Doxorubicin as a reference drug with IC(50) value (32.02 µM), while compound 14 is nearly as active as Doxorubicin as positive control.

Design and synthesis of some novel hydrazide, 1,2-dihydropyridine, chromene derivatives carrying biologically active sulfone moieties with potential anticancer activity.

This paper describes the synthesis of some novel sulfones having biologically active hydrazides (4-9, 22, 23, 26 and 27), hydrazonoyl cyanide (24), 1,2-dihydropyridines (16-21), chromene (28) and benzochromene (29) moieties starting with 1-[4-(piperidin-1-ylsulfonyl)phenyl]-ethanone 1. The structures of the the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR and 13C NMR. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (MCF7).