Structure–activity relationships in platelet-activating factor. Part 13: Synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 or pure antiretroviral activity

Serradji, Nawal; Bensaid, Okkacha; Martín, Marc; Sallem, Wafa; Dereuddre‐Bosquet, Nathalie; Benmehdi, Houcine; Redeuilh, Catherine; Lamouri, Aazdine; Dive, Georges; Clayette, Pascal; Heymans, Françoise

doi:10.1016/j.bmc.2006.07.031

Cited by 16 publications

(19 citation statements)

References 26 publications

(57 reference statements)

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“…20 Coupling 1 and 2 with commercial heterocyclic acid (HetCOOH), in the presence of DCC or DIC, led to the heteroarylamide piperazine derivatives 3a-j and 4a-f. The N-methylation of 3a and 4a using iodomethane and K 2 CO 3 in acetonitrile gave 3k and 4k, respectively.…”

Section: Chemistrymentioning

confidence: 99%

“…[18][19][20] All the results obtained are listed in Tables 1-3. Our initial synthetic efforts focused on determining the influence of the heterocyclic substitution position on the dual activity.…”

Section: Anti-paf and Anti-hiv Effectsmentioning

confidence: 99%

“…A previous work underlined the positive effects of the introduction of a benzyl or a 3,4,5-trimethoxybenzyl group instead of a 3,4,5-trimethoxybenzoyl moiety on the antiviral activity (Table 3, compounds A and B). 20 To see whether this observation was available in the heterocyclic series, we synthesized the compounds listed in Table 3. All bear an indole and a benzyl or a 3,4, 5-trimethoxybenzyl group on the piperazine.…”

Section: Anti-paf and Anti-hiv Effectsmentioning

confidence: 99%

“…18 All the modifications undertaken in order to improve its dual activity have been realized by either replacing the carbamate group of PMS 601 by other functions 19 or introducing an aromatic group on one or both nitrogens of the piperazine ring. 20 Those studies showed that more potent compounds than PMS 601 can be obtained and denote the absence of correlation between both anti-PAF and anti-HIV activities. Moreover, PMS 601 and Delavirdine (Rescriptor Ò , Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the second trimethoxybenzoyl substituent of PMS 601 was replaced by a benzyl or a 3,4,5-trimethoxybenzyl group since a previous study showed that compounds with a benzylic moiety exhibit higher antiviral activities than our reference compound. 20 All compounds were tested in vitro to evaluate their anti-PAF and anti-HIV-1 activities. The 3D electrostatic potential maps of certain compounds were also calculated to understand their anti-PAF activity.…”

Section: Introductionmentioning

confidence: 99%

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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

Sallem

Serradji

Dereuddre‐Bosquet

et al. 2006

Bioorganic & Medicinal Chemistry

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Abstract-As HIV-associated dementia prevalence has risen with the lifespan of HIV-infected individuals, there is an important need for antiretroviral and anti-inflammatory drugs targeting the central nervous system. Platelet-activating factor, a mediator of inflammation, is an HIV-induced neurotoxin secreted in the infected brain. In this work, we developed piperazine derivatives bearing a heterocyclic moiety as PAF-antagonists and HIV-1 replication inhibitors with micromolar potency.

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Section: Chemistrymentioning

confidence: 99%

Section: Anti-paf and Anti-hiv Effectsmentioning

confidence: 99%

Section: Anti-paf and Anti-hiv Effectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Sallem

Serradji

Dereuddre‐Bosquet

et al. 2006

Bioorganic & Medicinal Chemistry

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Random and Rational Approaches to HIV Drug Discovery in Africa

Hewer

Kriel

Coates

2012

Drug Discovery in Africa

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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 13: Synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 or pure antiretroviral activity

Cited by 16 publications

References 26 publications

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

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

Random and Rational Approaches to HIV Drug Discovery in Africa

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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