Magda A. El-Sherbeny

Synthesis, antimicrobial and antiviral evaluation of certain thienopyrimidine derivatives

Summary A series of 2-substituted amino-3-aminocyclopenteno or cyclohexeno[ b ]thieno[2,3- d ]-3,4-dihydropyrimidin-4-ones has been synthesized by reacting the corresponding thioureido derivatives with hydrazine hydrate. The thienoprimidine analogues obtained were further used to prepare their arylideneamino, thienotriazolopyrimidine or 2-methylthienotriazolopyrimidine derivatives. The prepared compounds were screened for antimicrobial, antiviral and cytotoxic activity. Some of the tested compounds showed promising activity. Detailed syntheses and spectroscopic and biological data are reported.

Synthesis and Antitumor Evaluation of Novel Cyclic Arylsulfonylureas: ADME-T and Pharmacophore Prediction

Novel derivatives of 5-(substituted)benzylidene-3-(4-substituted)phenylsulfonylimidazolidine-2,4-diones (3a-r), 1-(4-substituted)phenylsulfonyl-3-(4-substituted)phenylpyrimidine-2,4,6-(1H,3H,5H)-triones (6a-l), and 3-(4-substituted)phenyl-1-(4-substituted)phenylsulfonylquinazoline-2,4(1H,3H)- diones (8a-l) have been synthesized and tested for their antitumor activity against 60 tumor cell lines taken from 9 different organs. The tested compounds have showed good inhibitory effect at the ovarian cancer (IGROV1) cell line. A significant inhibition for (RXF393) renal cancer cells was observed with series 3 compounds, while in the other two series 6 and 8, there was a significant inhibition of ovarian cancer cells (OVCAR-8) and melanoma cells (SK-MEL-2). Interestingly; beside the strong inhibition of compound 3q to IGROV1 and RXF393 cells, a great inhibition (199.62%) for (M14) Melanoma cells was observed at the tested concentration (10 microM). ADME-T and pharmacophore prediction methodology were used to study the antitumor activity of the most active compounds and to identify the structural features required for antitumor activity.

Synthesis and biological evaluation of new curcumin derivatives as antioxidant and antitumor agents

Twenty-four new compounds were prepared, taking curcumin as a lead, in order to explore their antioxidant and antitumor properties. The capacities of these derivatives to scavenge the 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS.+), and to protect human red blood cells (RBCs) from oxidative haemolysis were investigated. In addition, the percentage viability of different cell lines (Hep G2, WI38, VERO and MCF-7) was tested. The result of the antitumor testing was generally in accordance with those of the antioxidant assays. Compounds which bear o-methoxy substitution to the 4-hydroxy function in the phenyl ring (7g, 5g and 3g) exhibited significantly higher ABTS.+-scavenging, antihaemolysis, and antitumor activities than other derivatives. In addition, molecular modelling studies were carried out for biologically active and inactive compounds, to study the structure–activity relationship, with the aim to elucidate which portions of the molecules are critical for the antioxidant and antitumor activity.

Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibition activities and molecular docking study of pyrazoline derivatives

Design, synthesis and pharmacological activities of a group of 1,3,5-trisubstituted pyrazolines were reported. The chemical structures of the synthesized compounds have been assigned on the basis of IR, MS, (1)H NMR, and (13)C NMR spectral analyses. The synthesized 1,3,5-trisubstituted pyrazoline derivatives were evaluated in vivo for anti-inflammatory, analgesic activities and in vitro for COX-1/2 inhibition assay. Among the tested compounds, derivatives 4h, 6e, 7a, 7e, and 9 showed more potent anti-inflammatory and analgesic activities than the reference drug celecoxib. On the basis of their higher activities in the in vivo studies compared with celecoxib, the five compounds 4h, 6e, 7a, 7e and 9 were selected to test their inhibitory activities against ovine COX-1/2 using an in vitro cyclooxygenase inhibition assay. Docking study of compounds 7a, 7e and 9 into the COX-2 binding site revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.

Synthesis, molecular modeling study, preliminary antibacterial, and antitumor evaluation of N-substituted naphthalimides and their structural analogues

Carboxylic acid imides 1–26 have been synthesized and screened for their antibacterial against gram-positive and gram-negative organisms and their antitumor activity against 60 tumor cell lines taken from nine different organs. Compounds 12, 14, and 16 were the most active and broad-spectrum antibacterial member in this study. Compound 9 showed the most cytotoxicity with a significant inhibition for renal cancer cells. 2D-QSAR study provides details on the fine relationship linking structure and activity and offers clues for structural modifications that can improve the activity. Docking study of the compounds 12, 14, and 16 into the active site of the topoisomerase II DNA gyrase enzymes revealed a similar binding mode to bound inhibitor Clorobiocin.Graphical Abstract

N-(12-Amino-9,10-di­hydro-9,10-ethano­anthracen-11-yl)-4-methyl­benzene­sulfonamide

The title compound, C23H22N2O2S, crystallizes with the 4-methylbenzenesulfonamide entity oriented towards the center of the bridgehead C atoms with a C—N—S—C torsion angle of −61.3 (2)°. The molecule features an intramolecular N—H⋯N hydrogen bond. Weak C—H⋯O and C—H⋯π interactions aid in forming the three-dimensional supramolecular structure.

4-[(1,3-Dioxoisoindolin-2-yl)meth­yl]benzene­sulfonamide

The title compound, C15H12N2O4S, is V-shaped with the isoindoline ring system (r.m.s. deviation = 0.006 Å) inclined to the benzene ring by 84.27 (13)°. In the crystal, inversion dimers are formed via pairwise N—H⋯O hydrogen bonds. These dimers associate further into corrugated ribbons, via pairwise N—H⋯O and C—H⋯O hydrogen bonds, propagating along the a-axis direction and lying parallel to (001).

Crystal, molecular structure, and conformational preferences of 3-(2-(4-morpholinophenyl)-2-oxoethyl)-5,5-diphenylimidazolidine-2,4-dione

ABSTRACT The X-ray crystal structure of 3-(2-(4-morpholinophenyl)-2-oxoethyl)-5,5-diphenylimidazolidine-2,4-dione (2) [C27H25N3O4: MF = 455.50, monoclinic, P21/c, a = 6.2038 (2) Å, b = 20.8905 (6) Å, c = 18.3361 (6) Å, b = 97.594 (2)ο, V = 2355.53 Å3, Z = 4, Dcalc = 1.284 Mg m−3, λ = 1.54178 Å] was determined. The crystal packing confirmed the occurrence of two conformers of opposite conformation. Conformational aspects of compound 2 have pointed out two factors that determine the conformation of the system under investigation: first, the intermolecular hydrogen bonding of the crystal packing, which stabilizes and favors the occurrence of two independent molecules, and the second factor is the steric hindrance among substituents.

(11R,12S)-16-Amino­tetra­cyclo­[6.6.2.02,7.09,14]hexa­deca-2(7),3,5,9(14),10,12-hexaen-15-ol

In the title compound, C16H15NO, the dihedral angle between the outer benzene rings is 51.88 (6)°, and each of the central six-membered rings has a boat conformation. The hydroxy and amino groups are syn, and the hydroxy H atom forms an intramolecular O—H⋯N hydrogen bond. In the crystal, molecules assemble via C—H⋯O and C—H⋯π interactions, consolidating a three-dimensional architecture.

N-(3-Amino-bicyclo-[2.2.1]heptan-2-yl)-4-methyl-benzene-sulfonamide.

In the title compound, C14H20N2O2S, the sulfonamide O atoms lie to one side of the benzene ring and the aminobicycloheptanyl to the other side [Car—S—N—C torsion angle = −57.93 (11)°; ar = aromatic]. An intramolecular N—H⋯N hydrogen bond is formed. In the crystal, a supramolecular chain is formed along the b axis via N—H⋯O and N—H⋯N hydrogen bonds.