Structure–activity relationships in platelet-activating factor. Part 14: Synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 activity

Sallem, Wafa; Serradji, Nawal; Dereuddre‐Bosquet, Nathalie; Dive, Georges; Clayette, Pascal; Heymans, Françoise

doi:10.1016/j.bmc.2006.07.043

Cited by 19 publications

(9 citation statements)

References 25 publications

(28 reference statements)

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“…Other studies have been focused on synthetically-produced PAF-inhibitors [39] that have been tested in several significant pathological situations [39,41]. Several of these molecules, either from natural origin such as ginkgolides A and B or synthetic ones such as roupatadine have already been used for the treatment of inflammatory pathological manifestations where PAF is implicated [39].…”

Section: Paf-inhibitorsmentioning

confidence: 99%

The Implication of Platelet Activating Factor in Cancer Growth and Metastasis: Potent Beneficial Role of PAF-Inhibitors and Antioxidants

Τσούπρας¹,

Iatrou

Frangia

et al. 2009

IDDT

138

169

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Cancer is one of the leading causes of death in Europe and United States. New blood vessel formation penetrating into solid tumors seems to be required for their growth and metastasis. Several protein growth factors can induce endothelial cell proliferation and angiogenesis, through signal transduction cascades that result in the production of several inflammatory mediators and lipid second messengers such as prostaglandins and Platelet Activating Factor (PAF). PAF is a potent mediator of inflammation that is implicated in several inflammatory pathological conditions such as atherosclerosis, cardiovascular and renal diseases, allergy, AIDS, cancer etc. It exerts its biological activities through G-protein-coupled receptors. The presence of PAF in the microenvironment of tumors may be due to its synthesis from circulating and / or cancer cells. Moreover, cancer cells and activated endothelial cells expose PAF-receptor on their membrane surface. PAF binding on its receptor induces several pathways that result in the onset and development of tumor induced angiogenesis and metastasis. PAF-receptor antagonists have exhibited promising results in vitro and in vivo as anti-angiogenic molecules in several cancer cells and tumors. A dietary profile reach in antioxidants and PAF-inhibitors (such as the Mediterranean Diet) may provide beneficial preventive and protective effects against development, growth and metastatic manifestations of cancer cells, through either their inhibition of PAF activity and / or its biosynthesis. The clarification of factors that may down regulate pathologically increased PAF-levels in a tumor microenvironment may also contribute to the planning of a potent nontoxic preventive and therapeutic approach against cancer.

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Section: Paf-inhibitorsmentioning

confidence: 99%

The Implication of Platelet Activating Factor in Cancer Growth and Metastasis: Potent Beneficial Role of PAF-Inhibitors and Antioxidants

Τσούπρας¹,

Iatrou

Frangia

et al. 2009

IDDT

138

169

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“…Others include the possible HIV-1 neurotoxin platelet-activating factor (PAF) (45), as well as soluble VCAM and von Willebrand factor (42, 43). HAART has been shown to reduce the latter two markers in HIV-1-infected patients (46, 47), but to have no effect on soluble platelet activation markers, including PAF acetylhydrolase (48) and sCD40-L (44).…”

Section: Hiv-associated Dementiamentioning

confidence: 99%

Soluble CD40 ligand in dementia

Giunta¹,

Figueroa²,

Town³

et al. 2009

Drugs Fut

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Some 15-20% of the population over the age of 65 years suffer from dementia, currently one of the leading causes of death behind cardiovascular diseases, cancer and cerebrovascular diseases. The major forms of dementia share in common overactivation of the CD40-CD40-L complex, leading to high levels of proinflammatory cytokine production by immune cells of the central nervous system (CNS), including microglia and astrocytes. Consequently, both neuronal survival and signaling are negatively affected, leading to the characteristic progressive loss of higher cortical functions. We have reviewed the literature concerning the involvement of this complex in the pathology of three major forms of dementia: Alzheimer's-type, HIV-associated and vascular dementia. This is followed by a discussion of current preclinical and clinical therapies that may influence this interaction, and thus point the way toward a future neuroimmunological approach to inhibiting the effects of CD40-CD40-L in neuropsychiatric disease.

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“…We have reported in the recent years the synthesis of a great number of tri-substituted piperazine which showed potent dual anti-PAF and anti-HIV-1 activities Sallem et al, 2006;Serradji et al, 2000;Serradji et al, 2006;Serradji et al, 2004). One of these compounds (PMS 601) has been demonstrated to be able to cross the blood-brain barrier and considered to be a promising candidates for HIV-associated dementia (HAD) therapy, taking into account the other very interesting properties of this molecule.…”

Section: Introductionmentioning

confidence: 98%

Apoptosis of Human Burkitt’s lymphoma cells induced by 2-N,N-Diethylaminocarbonyloxymethyl-1-diphenylmethyl-4-(3,4,5-trimethoxybenzoyl) piperazine hydrochloride (PMS-1077)

Wang

Chen

et al. 2009

Arch. Pharm. Res.

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Piperazine is one of the heterocycles which are associated with diverse pharmacological activities. 2-N,N-Diethylaminocarbonyloxymethyl-1-diphenylmethyl-4-(3,4,5-trimethoxybenzoyl) piperazine hydrochloride (PMS-1077) is a trisubstituted piperazine which contains a trimethoxybenzene ring and a benzhydrylpiperazine fragment, both of which can induce cell proliferation regression by different mechanisms. We have therefore examined the effects of PMS-1077 on Human Burkitt's lymphoma cells (Raji). The viability of Raji cells was determined by MTT assay and also assessed by trypan blue dye exclusion method. The results demonstrate that PMS-1077 can suppress the proliferation of Raji cells in a dose- and timedependent manner, while inhibit colony formation ability of Raji cells merely in a dose-dependent manner in vitro. Meanwhile, morphological changes were observed using fluorescence microscope. Flow cytometric analysis through PI stains showed that PMS-1077 blocked the growth of Raji cells in the G(0)/G(1) period, and induced apoptosis of Raji cells after 48 h of incubation. Cell apoptosis induced by PMS-1077 was further confirmed by staining with Annexin-V FITC and PI. Preliminary study by molecular docking suggests that PMS-1077 may inhibit tubulin polymerization. More experiments are in progress in our laboratory to reveal the mode of action of PMS-1077 in the induction of apoptosis of Raji cells.

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Structure–activity relationships in platelet-activating factor. Part 14: Synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 activity

Cited by 19 publications

References 25 publications

The Implication of Platelet Activating Factor in Cancer Growth and Metastasis: Potent Beneficial Role of PAF-Inhibitors and Antioxidants

The Implication of Platelet Activating Factor in Cancer Growth and Metastasis: Potent Beneficial Role of PAF-Inhibitors and Antioxidants

Soluble CD40 ligand in dementia

Apoptosis of Human Burkitt’s lymphoma cells induced by 2-N,N-Diethylaminocarbonyloxymethyl-1-diphenylmethyl-4-(3,4,5-trimethoxybenzoyl) piperazine hydrochloride (PMS-1077)

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