Mohamed Ghazzali

Design, synthesis and pharmacophoric model building of novel substituted nicotinic acid hydrazones with potential antiproliferative activity

Novel 6-aryl-2-methylnicotinic acid hydrazides 4a-c and their corresponding hydrazones 5a-c and 6a-i were synthesized. X-ray single crystal diffraction of 6h confirmed the chemical structure of hydrazones 6a-i. Antiproliferative activity of the synthetic compounds was investigated against K562 leukemia cell lines. Variable cell growth inhibitory activities were obtained with IC50 range from 24.99 to 66.78 μM where the compound 6c exhibited the maximum activity. Structure activity relationship analysis has been performed and a common pharmacophore model for the synthesized derivatives has been obtained by using the pharmacophore elucidation module of the software MOE. The best model obtained is characterized by two projected locations of potential H-bond donors (F 3 and F4) and two Aromatic annotations (F1 and F2).

Light-stable bis(norharmane)silver(I) compounds: Synthesis, characterization and antiproliferative effects in cancer cells

Four different-anion Ag(I) compounds with the ligand norharmane (9H-Pyrido[3,4-b]indole; Hnor) and having the general formula [Ag(Hnor)2](anion) (anion=ClO4(-), NO3(-) and BF4(-)) [Ag(Hnor)2(MeCN)](PF6) are reported, and studied in detail regarding their coordination mode and in vitro antiproliferative effects. X-ray structural analysis revealed that the complex with the PF6(-) anion has a MeCN solvent molecule weakly coordinated to Ag(I), making the metal coordination T-shaped, while the other compounds present the classical linear Ag(I) coordination. The compounds showed certain cell growth inhibitory effects in two different cancer cell lines, with the perchlorate containing complex being the most toxic and in fact comparable to cisplatin. Notably, the compounds are stable in visible light; and the luminescence in the solid state was found to be extremely weak, whereas in MeOH solution all compounds show a moderate to weak emission band at 375 nm, when excited at 290 nm.

Synthesis, structural chemistry and antimicrobial activity of −(−) borneol derivative

AbstractBorneol is a monoterpene that is a part of traditional Chinese and Japanese medicine. (−) borneol reacted with methanesulfonyl chloride in THF/pyridine to afford the new 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methane sulfonate derivative in excellent yield. The product is characterized by H1NMR, C13NMR, mass spectroscopy as well as elemental analysis and its structure was identified by X-ray single crystal diffraction. The packing of 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methanesulfonate exhibits the non-classical C-H···O hydrogen bonding in C(4) and R22(8) chain and ring motifs as structural determinants. This was also confirmed by the analysis of Hirshfeld surfaces. The 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methane sulfonate antimicrobial activity was tested and compared with its parent (−) borneol against three different pathogens. Particularly, 1,7,7-trimethylbicyclo[2.2.1]hept-2-yl methane sulfonate showed high sensitivity, compared to Chloramphenicol reference material, against Escherichia coli.

Insights into the strong in-vitro anticancer effects for bis(triphenylphosphane)iminium compounds having perchlorate, tetrafluoridoborate and bis(chlorido)argentate anions

Three new compounds containing the bis(triphenylphosphane)iminium cation (PPN(+)) with ClO4(-), BF4(-) and [AgCl2](-) as counter anions have been synthesized and structurally characterized. The two derivatives with ClO4(-) and BF4(-) were found to be isostructural by single crystal X-ray diffraction. Interestingly, the three compounds show extremely potent antiproliferative effects against the human cancer cell line SKOV3. To gain insights into the possible mechanisms of biological action, several intracellular targets have been considered. Thus, DNA binding has been evaluated, as well as the effects of the compounds on the mitochondrial function. Furthermore, the compounds have been tested as possible inhibitors of the seleno-enzyme thioredoxin reductase.

Multi-component self-assembly of molecule based materials by coordination networks and weak intermolecular synthons

The coordination polymer [Fe(SCN)2(1,2-bis(4-pyridylmethylene)hydrazine)2]n [Fe(phenanthroline)3]2n(ClO4)2n·n1,2-bis(4-pyridylmethylene)hydrazine·4nH2O 1 was crystallised from a MeOH/MeCN solution and the structure consists of layered (4,4) 2D-nets with supramolecular ([Fe(phen)3]2bphz)4+ units in the pores and disordered water and perchlorate anions. The same supramolecular motif could be independently prepared as [Fe(phen)3]2·bphz(ClO4)4·xMeOH 2, and the [Ru(phenanthroline)3]2+ compound 3, isostructural to 1, was also prepared although a complete structure determination was prevented by low crystal quality. Compounds 1 and 3 are rare examples of how several large and different components can be assembled inside a 2D coordination network and provide a concept for multi-component self-assembly.

N'-(Di-2-pyridylmethyl-ene)benzo-hydrazide.

In the title Schiff base, C18H14N4O, the amido –NH– unit is connected to one of the two pyridyl N atoms at an N(—H)⋯N distance of 2.624 (2) Å. The molecular packing features an intermolecular C—H⋯N R 2 2(6) hydrogen-bonding ring motif.

A three-dimensional net of Δ-tris(1,10-phenanthroline)ruthenium(II) in the dual-metal self-assembly of bis[tris(1,10-phenanthroline)ruthenium(II)] tetraisothiocyanatoiron(II) bis(perchlorate)

The title compound, [Ru(C(12)H(8)N(2))(3)](2)[Fe(NCS)(4)](ClO(4))(2), crystallizes in a tetragonal chiral space group (P4(1)2(1)2) and the assigned absolute configuration of the optically active molecules was unequivocally confirmed. The Delta-[Ru(II)(phen)(3)](2+) complex cations (phen is 1,10-phenanthroline) interact along the 4(1) screw axis parallel to the c axis, with an Ru...Ru distance of 10.4170 (6) A, and in the ab plane, with Ru...Ru distances of 10.0920 (6) and 10.0938 (6) A, defining a primitive cubic lattice. The Fe atom is situated on the twofold axis diagonal in the ab plane. The supramolecular architecture is supported by C-H...O interactions between the [Ru(II)(phen)(3)](2+) cation and the disordered perchlorate anion. This study adds to the relatively scarce knowledge about intermolecular interactions between [Ru(phen)(3)](2+) ions in the solid state, knowledge that eventually may also lead to a better understanding of the solution state interactions of this species; these are of immense interest because of the photochemical properties of these ions and their interactions with DNA.

Supramolecular assembly in metal complexes: Two structural cases

With the current advances in our understanding of molecular components in the solid-state world, the relation between energy and geometry remains controversial. In this study, we deliver a concise account for supramolecular chemistry, and in order to illustrate some of its concepts we describe some structural and theoretical analyses for two unique cases of our work. We elaborate on a supramolecular model of controlled “one-pot” host–guest metal-mediated self-assembly reaction inside iron coordination polymer grid architecture, and we review halogen bonding by specifically observing M–Cl···Cl–M intermolecular interactions using Cambridge Structural Database (CSD) hit analyses with theoretical calculations.

Facile synthesis of 3-substituted quinazoline-2,4-dione and 2,3-di-substituted quinazolinone derivatives

Abstract3-Substituted quinazoline-2,4(1H,3H)-dione and 2,3-di-substituted quinazolineone derivatives attract considerable interest due to their pharmacological properties. In this paper, we report the synthesis of N-substituted-3-nitrophthalimide derivatives II–III, the reactions of phthalimide III with amines, hydrazines, and amino acid derivatives to synthesise a small library of 3-substituted-5-nitroquinazoline-2,4(1H,3H)-diones IV–XIV and 2,3-di-substituted-6-nitro-quinazolineones XVIII–XIX.

An interpenetrating primitive cubic net formed by hydrogen bonds and coordination bonds in catena-poly[[bis(methanol-κO)bis(thiocyanato-κN)iron(II)]-μ-1,2-bis(4-pyridylmethylene)hydrazine-κ2N:N′]

In the title compound, [Fe(NCS)(2)(C(12)H(10)N(4))(CH(4)O)(2)](n), at 153 (2) K, the Fe atom is located on an inversion centre, as is the centre of the N-N bond in the ligand molecule. The structure contains a one-dimensional coordination polymer with an Fe...Fe distance of 15.866 (7) A and can be described as two interpenetrating six-connected primitive cubic (pcu) three-dimensional networks when additional intermolecular O-H...S hydrogen bonds are taken into account. The compound is not isostructural with the corresponding Mn(II) compound as they differ in the rotation around the M-O bond by 90 degrees , giving rise to completely different hydrogen-bond patterns. This study demonstrates the impact of conformational differences on the final supramolecular arrangement.