Mohammed Al-Ghorbani

Synthesis of oxadiazole-morpholine derivatives and manifestation of the repressed CD31 Microvessel Density (MVD) as tumoral angiogenic parameters in Dalton's Lymphoma.

A series of oxadiazole derivatives possessing morpholine 6a-l were synthesized by nucleophilic substitution reaction of key intermediates [1,3,4]-oxadiazole-2-thiol derivatives 5a-l with 4-(2-chloroethyl) morpholine. Compounds 6a-l were evaluated for their in vitro and in vivo antitumor potential in Daltons Lymphoma Ascites (DLA) tumor cells. Among 6a-l series, compound 6a with concentration ∼8.5μM have shown extensive cytotoxicity in vitro and 85% reduction in tumor volume in vivo, attributing an excellent anti-proliferative capability towards the cancer cells. Compound 6a has extensively inhibited the Microvessel Density (MVD) or tumoral neovasculature which was evident from the CD31 immuno staining and peritoneal H&E staining. The major reason for the antiproliferative activity of compound 6a was due to the repression of tumor vasculature.

Piperazine and morpholine:Synthetic preview and pharmaceutical applications

This review summarizes the in vitro and in vivo medicinal chemistry investigations for piperazine and morpholine analogues. Piperazine and morpholine nucleus show a broad spectrum of pharmaceutical applications, thus, in recent years scientists has developed various new methods for the synthesis of their derivatives. This review shows current tendency in the piperazine and morpholine analogues synthesis and reveals their potent pharmacophoric activities.

Synthesis and antiproliferative activity of benzophenone tagged pyridine analogues towards activation of caspase activated DNase mediated nuclear fragmentation in Dalton’s lymphoma

A series of benzophenones possessing pyridine nucleus 8a-l were synthesized by multistep reaction sequence and evaluated for antiproliferative activity against DLA cells by in vitro and in vivo studies. The results suggested that, compounds 8b with fluoro group and 8e with chloro substituent at the benzoyl ring of benzophenone scaffold as well as pyridine ring with hydroxy group exhibited significant activity. Further investigation in mouse model suggests that compounds 8b and 8e have the potency to activate caspase activated DNase (endonuclease) which is responsible for DNA fragmentation, a primary hallmark of apoptosis and thereby inhibits the Daltons lymphoma ascites tumour growth.

Synthesis and biological evaluation of salicylic acid conjugated isoxazoline analogues on immune cell proliferation and angiogenesis

Mitogenicity is the ability of the natural or synthetic compounds to induce cell division or proliferation. A series of salicylic acid derivatives containing isoxazoline moiety (8a-j) were synthesized and their immunopharmacological activities targeting lymphocyte proliferation and angiogenesis were evaluated. The compounds 8a-j mitogenicity were investigated on immunological cells that include human peripheral blood lymphocytes and murine splenocytes in-vitro. The results implicate that among the series of 8a-j, compound 8e showed a potent proliferative response on both human and murine lymphocytes. The proliferative index of the compound 8e was comparable to the reference mitogen Con A and mitogenecity is due to increased secretion IL-2. In -vivo CAM and rat corneal angiogenesis assays were performed to assess the compounds effect on endothelial cell migration and proliferation which inferred that 8e also induces the proliferation of endothelial cells. The study reports the synthetic immunostimulatory and pro-angiogenic activity of novel mitogen 8e which could be translated into new drug in future.

SYNTHESIS AND BIOLOGICAL EFFICACY OF NOVEL PIPERAZINE ANALOGUES BEARING QUINOLINE AND PYRIDINE MOIETIES.

A series of novel piperazine analogues bearing quinolin-8-yloxy-butan-1-ones/pyridin-2-yloxyethanones were synthesized by a simple and convenient approach based on various substituted piperazine incorporating quinoline and pyridine moieties. The analogues were evaluated for in vitro antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferrous ion radical scavenging activities and anti-inflammatory activity by inhibition of Vipera russelli venom (PLA2) and gastric K+/H+-ATPase activities. Most of the title compounds exhibited promising activity. Best antioxidant and PLA2-inhibiting activities were found for piperazine analogues with phenyl and nitro phenyl groups, whereas methoxy group on phenyl piperazine indicated selectivity for the H+/K+-ATPase.

Evaluation of Benzophenone-N-ethyl Morpholine Ethers as Antibacterial and Antifungal Activities

Microorganisms are closely associated with the health and welfare of human beings. Whereas some microorganisms are beneficial, others are detrimental. Bacterial infections often produce inflammation and pains and in some instances, infections result in high mortality. Any subtle change in the drug molecule, which may not be detected by chemical methods, can be revealed by a change in the antimicrobial activity and hence microbiological assays are very useful. A series of substituted hydroxy benzophenones and benzophenone-N-ethyl morpholine ethers were screened for their antibacterial and antifungal activities. Antibacterial activity against S. aureus, E. aerogenes, M. luteus, K. pneumonia, and S. typhimurium, S. paratyphi-B and P. vulgaris bacterial strains and antifungal activity against C. albicans, B. cinerea, M. pachydermatis, C. krusei fungal strains were carried out. The bioassays indicated that most of the synthesized compounds showed potential antibacterial and antifungal agents.

2-Benzoyl-4-chloro\-phenyl benzoate

In the title compound, C20H13ClO3, the dihedral angles between the benzoate and the chlorobenzene and benzoyl rings are 68.82 (5) and 53.76 (6)°, respectively, while the dihedral angle between the benzoyl and benzoate rings is 81.17 (5)°. The eight atoms of the benzoyl residue are essentially planar with the exception of the O atom which lies 0.1860 (5) Å out of their mean plane (r.m.s. deviation = 0.97 Å). The nine atoms of benzoate residue are also essentially planar (r.m.s. deviation = 0.20 Å) with the ester O atom showing the greatest deviation [0.407 (12) Å] from their mean plane. In the crystal, molecules are connected into centrosymmetric dimers by pairs of C—H⋯O hydrogen bonds.