Donald Poirier

Donald Poirier
Laval University | ULAVAL · Department of Molecular Medicine

About

422
Publications
16,715
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6,593
Citations
Citations since 2017
68 Research Items
1807 Citations
2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
2017201820192020202120222023050100150200250300
Introduction
Skills and Expertise

Publications

Publications (422)
Article
Full-text available
Estradiol (E2) plays an important role in the progression of diseases such as breast cancer and endometriosis. Inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), the enzyme that catalyzes the last step in the biosynthesis of the estrogenic hormone E2, therefore constitutes an interesting approach for the treatment of these two estrog...
Patent
Derivatives of 10S, 17S- diHDA (protectin DX, PDX) and medicinal uses thereof are disclosed. These derivatives are specialized pro- resolving mediators (SPRMs) . In specific embodiments, said derivatives. are used in to prevent or treat viral infections (including influenza and coronavirus infections) , insulin resistance, diabetes, and inflammator...
Patent
Full-text available
Novel chem. agents are described herein. More specifically, a novel inhibitor of 17β-HSD7 for decreasing estradiol concns. while restoring dihydrotestosterone (DHT) concns. in breast cancer cells is disclosed herein. In a particular embodiment, the inhibitor of 17β-HSD7 has the following structure: (Formula I) A process for producing the novel inhi...
Article
17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2) may be involved in the local modulation of estradiol (E2) availability in adipose tissues. Objective: To assess the conversion of E2 into estrone (E1) as well as the expression of 17β-HSD2 and its localization in omental (OM) and subcutaneous (SC) adipose tissues obtained from women. Methods: R...
Article
Prostate cancer is the most common cancer among men and the development of new therapeutic agents is needed for its treatment and/or diagnosis. 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is involved in the production of androgens, which stimulates the proliferation of prostate cancer cells. Piperazinomethyl-androsterone sulfonamide derivati...
Article
Endometriosis is a gynecological disorder affecting about 10% of women and can lead to invalidating painful symptoms and infertility. Since there is no current, definitive cure for this disease, new therapeutic options are necessary. 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is involved in the production of estradiol (E2), the most potent...
Article
Cancer remains one of the leading causes of death, worldwide. In addition, the lack of efficacy and selectivity of chemotherapeutic agents for cancer cells is a challenge that needs to be addressed through the development of new drugs. Since aminosteroids are of interest in fighting cancer, our group previously reported antiproliferative activity o...
Article
Full-text available
Aim and objective: The syntheses of glucuronide metabolites of phenolic xenoestrogens triclosan and 2-phenylphenol, namely triclosan-O-glucuronide (TCS-G; 1), and 2-phenylphenol-O-glucuronide (OPP-G; 2), were achieved for use as analytical standards. Methods: Under classical conditions previously reported for glucuronide synthesis, the final bas...
Patent
Full-text available
A method for the synthesis of specialized pro- resolving mediators, structural isomers thereof and analogs thereof is disclosed herein. The method comprises reacting a compd. of the formula (I) : (I) wherein R1 is alkyl(C≤12) , cycloalkyl(C≤12) , alkenyl(C≤12) , alkylidene(C≤12) , alkynyl(C≤12) , aryl, aralkyl, heteroaryl or heteroaralkyl; and X1,...
Article
Full-text available
Aminosteroid derivative RM-581 was previously identified as an endoplasmic-reticulum (ER) stress inducer with potent in vitro and in vivo anticancer activities. We report its evaluation in androgen-independent prostate cancer (PC-3) cells. RM-581 efficiently blocks PC-3 cell proliferation with stronger activity than that of a selection of known ant...
Article
Human 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7), a special multifunctional enzyme, activates the estrogen estrone while inactivating the potent androgen dihydrotestosterone. Thus, this enzyme has become an ideal target for hormone-dependent breast cancer treatment, as its inhibition leads to estradiol reduction and dihydrotestosterone rest...
Article
17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) and steroid sulfatase (STS) are involved in the synthesis of the most potent estrogen in the human body, estradiol (E2). These enzymes are known to play a pivotal role in the progression of estrogen-dependent diseases, such as breast cancer and endometriosis. Therefore, the inhibition of 17β-HSD1 a...
Article
RM-581 is an aminosteroid derivative comprised of a steroid core and a quinoline side chain showing potent cytotoxic activity on several types of cancer cells but for which the mechanism of action (MoA) remains to be fully elucidated. The opportunity to turn RM-581 into a fluorescent probe was explored because the addition of a N-dimethyl group was...
Article
Full-text available
17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) plays an important role in estrogen-dependent breast tumor growth. In addition to being involved in the production of estradiol (E2), the most potent estrogen in women, 17β-HSD1 is also responsible for the production of 5-androsten-3β,17β-diol (5-diol), a weaker estrogen than E2, but whose importan...
Article
A new androsterone derivative bearing a 16β-picolyl moiety (compound 5; FCO-586-119) was synthetized in four steps from the lead compound 1 (RM-532-105). We measured its inhibitory activity on 17β-HSD3 using microsomal fraction of rat testes as well as transfected LNCaP[17β-HSD3] cells. We then assessed its metabolic stability as well as its cytoto...
Article
Full-text available
The combination of an androstane-3,17-diol nucleus and a 2β-N-alkylamidopiperazino sidechain is important for the anticancer activity of a new family of steroid derivatives. As the structure-activity relationship studies have so far been limited to the beta orientation of the substituent at position 2 of the steroid nucleus, a series of analogs (co...
Article
17beta-Hydroxysteroid dehydrogenase type 10 (17β-HSD10) is the only mitochondrial member of 17β-HSD family. This enzyme can oxidize estradiol (E2) into estrone (E1), thus reducing concentration of this neuroprotective steroid. Since 17β-HSD10 possesses properties that suggest a possible role in Alzheimer’s disease, its inhibition appears to be a th...
Article
Background The last step in the production of androgen testosterone from 4-androstene-3,17-dione (4-dione) in testis involves the 17-hydroxysteroid dehydrogenase type 3 (17-HSD3). Blocking this microsomal enzyme with an inhibitor would lower the level of testosterone and, consequently, could be an approach for the treatment of androgen-dependent...
Article
The main objective of this study was to extract the essential oils from Clerodendrum formicarum and Syzygium cordatum in order to determine the anticancer activity and establish the chemical constituents of that kind of essential oils. Hence, we have used hydrodistillation method to obtain the desired extracts or samples of essential oils. Indeed,...
Article
Steroid sulfatase (STS) is an important enzyme regulating the conversion of sulfated steroids into their active hydroxylated forms. Notably, the inhibition of STS has been shown to decrease the levels of active estrogens and was translated into clinical trials for the treatment of breast cancer. Based on quantitative structure-activity relationship...
Article
The use of new aminosteroids has shown increased therapeutic efficiency on multiple cancer cell lines. Those molecules are, however, highly hydrophobic, leading to bad pharma-cokinetic properties. Dendrimers are excellent candidates to improve PK, especially for absorption and distribution, since their structure can be designed to be water-soluble....
Article
The use of new aminosteroids has shown increased therapeutic efficiency on multiple cancer cell lines. Those molecules are, however, highly hydrophobic, leading to bad pharmacokinetic properties. Dendrimers are excellent candidates to improve PK, especially for absorption and distribution, since their structure can be designed to be water‐soluble....
Article
The aminosteroid (AM) RM-581 is built around a mestranol backbone and has recently emerged as this family's lead candidate, showing in vitro and in vivo potency over different types of cancer, including high fatality pancreatic cancer. To extend the structure-activity relationships (SAR) to other estrane analogs, we synthesized a focused series of...
Article
5α-Dihydrotestosterone (5α-DHT) possesses a great affinity for the androgen receptor (AR), and its binding to AR promotes the proliferation of prostate cancer (PC) cells in androgen-dependent PC. Primarily synthesized from testosterone (T) in testis, 5α-DHT could also be produced from 5α-androstane-3α,17β-diol (3α-diol), an almost inactive androgen...
Article
Efforts toward the development of a reliable gram scale synthesis of PBRM, a potent and selective steroidal covalent inhibitor of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), are described. Among the three synthetic routes (C-E) developed herein, route E is the most efficient one with only 6 chemical steps from commercially available estrone...
Article
Decreasing the intratumoral androgen biosynthesis by using an inhibitor of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a strategy to treat prostate cancer. The androsterone (ADT) derivative 1 (RM-532-105) has shown strong inhibitory activity on 17β-HSD3, but needs to be improved. Herein, we describe the chemical synthesis and characteriza...
Presentation
The first total synthesis of a lipid mediator derived from natural omega-3-fatty acid docosahexaenoic acid (DHA), 10S,17S-diHDHA (also referred to as protectin DX/PDX) was achieved in a convergent route (29 steps). The two chiral hydroxyl groups at C-10 and C-17 were derived from readily available (S)-1,2,4-butanetriol and (R)-glycidol, respectivel...
Presentation
Cancer is responsible for one in four deaths in Canada. In fact, despite the large number of available cancer-treating drugs, new ones, acting differently by different mechanisms, need to be developed to overcome drug resistance and improve overall survival rate. Based on structure-activity relationship (SAR) studies, we developed two closely relat...
Conference Paper
Full-text available
Aminosteroid (AM) derivatives are a new family of pro-apoptotic anticancer compounds inducing endoplasmic reticulum stress via disturbance of cholesterol homeostasis. RM-581, built around a mestranol backbone, has recently emerged as the lead candidate of this family and shown in vitro and in vivo potency over different cancer types, including high...
Conference Paper
Decreasing the intratumoral androgen biosynthesis by using an inhibitor of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a strategy to treat prostate cancer. The androsterone (ADT) derivative 1 (RM-532-105) has shown strong inhibitory activity on 17β-HSD3, but needs to be improved. Herein, we describe the chemical synthesis of two series of...
Presentation
The development of a reliable multigram synthesis of PBRM, a potent and selective steroidal covalent inhibitor of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), has been efficiently achieved. Among the four synthetic routes (A-D) developed, route D is by far the most efficient one with only 6 chemical steps from commercially available estrone,...
Article
Full-text available
The high fatality and morbidity of pancreatic cancer have remained almost unchanged over the last decades and new clinical therapeutic tools are urgently needed. We determined the cytotoxic activity of aminosteroid derivatives RM-133 (androstane) and RM-581 (estrane) in three human pancreatic cancer cell lines (BxPC3, Hs766T and PANC-1). In PANC-1,...
Conference Paper
Les dérivés d'aminostéroïdes (AM) constituent une nouvelle famille de composés anticancéreux pro-apoptotiques induisant un stress du réticulum endoplasmique (RE) via une perturbation de l'homéostasie du cholestérol. Le RM-581, construit autour d'un squelette de mestranol, est récemment devenu le candidat principal de cette famille et a démontré de...
Presentation
La stéroide sulfatase (STS) est une enzyme clé impliquée dans la biosynthèse des estrogènes et des androgènes car elle catalyse l’hydrolyse des stéroïdes sulfatés (CHOLS, DHEA-S, PREG-S, E1-S et E2-S) en leurs correspondants non sulfatés, précurseurs des hormones actives. De ce fait, la STS constitue une cible thérapeutique intéressante pour traite...
Conference Paper
Le cancer du sein est le cancer le plus fréquent chez les femmes, à l'exception des cancers de la peau et la deuxième cause de décès par cancer. Parmi les patientes atteintes du cancer du sein, environ 65% ont un cancer hormono-dépendant, ce qui signifie que plus de la moitié des cancers du sein sont susceptibles de réagir positivement à un traitem...
Article
Steroid sulfatase (STS) is a key enzyme involved in the biosynthesis of estrogens from inactive sulfated steroids. After we reported EO-33 as a potent in vitro STS inhibitor without undesirable estrogenic activity and with osteogenic properties, we are now interested in validating EO-33’s in vivo potential to inhibit STS, to prevent bone deteriorat...
Article
Estrogen-receptor related receptors (ERRs)which consists of ERRα, ERRβ and ERRγ belong to the orphan nuclear receptor subfamily 3, group B (NR3B)subfamily, and are constitutively active. ERRs have been shown to actively modulate estrogenic responses, and to play an essential role in pregnancy, and are implicated in breast cancer progression. Despit...
Article
Full-text available
The first total synthesis of a lipid mediator derived from natural ω-3-fatty acid docosahexaenoic acid (DHA), 10S,17S-diHDHA (also referred to as protectin DX/PDX), was achieved in a convergent route (29 steps). The two chiral hydroxyl groups at C-10 and C-17 were derived from readily available (S)-1,2,4-butanetriol and (R)-glycidol, respectively....
Article
Cytochrome P450 (CYP) 1B1 is involved in the bioactivation of procarcinogens and drug-resistance. To obtain selective CYP1B1 inhibitors overs CYP1A1, we synthesized four series of estrane derivatives: 1) twelve estrone (E1)- and 17β-estradiol (E2)-derivatives bearing a 3- or a 4-pyridinyl core at C2, C3, or C4, 2) eight estrane derivatives with dif...
Article
17β-Hydroxysteroid dehydrogenase type 10 (17β-HSD10) is a mitochondrial enzyme known for its potential role in Alzheimer's Disease (AD). 17β-HSD10, by its oxidative activity, could decrease the concentration of two important neurosteroids, allopregnanolone (ALLOP) and 17β-estradiol (E2), respectively preventing their neurogenesis and neuroprotectiv...
Article
17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a promising therapeutic target known to play a pivotal role in the progression of estrogen-dependent diseases such as breast cancer, and endometriosis. This enzyme is responsible for the last step in the biosynthesis of the most potent estrogen, estradiol (E2) and its inhibition would prevent th...
Article
17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) plays a pivotal role in the progression of estrogen-related diseases due to its involvement in the biosynthesis of estradiol (E2), constituting a valuable therapeutic target for endocrine treatment. In the present study, we successfully co-crystallized the enzyme with the reversible inhibitor 2-met...
Article
Full-text available
17β-Hydroxysteroid dehydrogenase type 10 (17β-HSD10) is a steroidogenesis enzyme known for its potential role in Alzheimer’s disease. For comparison purposes between steroidal and nonsteroidal 17β-HSD10 inhibitors 1 and 2, respectively, we attempted the chemical synthesis of benzothiazole phosphonate derivative 2. Instead of a one-pot synthesis, we...
Article
Steroid sulfatase is detectable in most hormone-dependent breast cancers. STX64, an STS inhibitor, induced tumor reduction in animal assay. Despite success in phase І clinical trial, the results of phase II trial were not that significant. Breast Cancer epithelial cells (MCF-7 and T47D) were treated with two STS inhibitors (STX64 and EM1913). Cell...
Article
Background: RM-133 belongs to a new family of aminosteroid derivatives demonstrating interesting anticancer properties, as confirmed in vivo in four mouse cancer xenograft models. However, the metabolic stability of RM-133 needs to be improved. After investigation, the replacement of its androstane scaffold by a more stable estrane scaffold led to...
Article
The development of a covalent inhibitor of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a promising approach for the treatment of hormone-dependent breast cancer and endometriosis. After reporting the steroid derivative PBRM as a first potent covalent inhibitor of 17β-HSD1 without estrogenic activity, we are now interested in studying its...
Article
Full-text available
The fortuitous modification of a quinoline-proline-piperazine side chain linked to a steroid in the presence of lithium (trimethylsilyl) acetylide has generated an unknown product that is more active than its precursor. After having characterized two β-enaminones (two-carbon homologation compounds) that were generated from a simplified model side c...
Article
Aim and Objective: The development of small molecules that can interact with key therapeutic target represents an active field of research. Therefore, new approaches for increasing the molecular diversity of a starting material, such as a natural product, are needed. Herein, the carbonyl group present on a pregnane scaffold, or easily obtained from...
Article
Inhibition of cytochrome P450 (CYP) 1B1 is a promising therapeutic strategy, as such an inhibitor could modulate the bioactivation of procarcinogens while reducing drug resistance. Based on docking studies, the synthesis of 12 estra-1,3,5(10)-triene derivatives containing a pyridin-3-/4-yl moiety at position C2, 3 or 4 was performed and we measured...
Conference Paper
Prostate Cancer (PCa) has been a major public health concern in North America since it is the second most common cancer in men. Although there are currently several hormonal therapies to improve health or prolong life expectancy, PCa often evolves into a resistant form. The androgen receptor (AR) signaling pathway plays a central role in PCa develo...
Article
17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) is involved in the biosynthesis of estradiol, the major bioactive endogenous estrogen in mammals, and constitutes an interesting therapeutic target for estrogen-dependent diseases. A steroidal derivative, 3-{[(16β,17β)-3-(2-bromoethyl)-17-hydroxyestra-1,3,5(10)-trien-16-yl]methyl} benzamide (PBRM),...
Article
Full-text available
This study was to develop green methodology to convert vegetable oils into ethyl esters of fatty acids using lemon juice (pH=2.8) as a natural catalyst and ethanol as reagent. It is a first application of lemon juice to synthesize ethyl esters from fatty acids of vegetable oils. We used the sulfuric acid as a control to compare the catalytic activi...
Article
Human cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of various drugs. This enzyme catalyzes the hydroxylation of aryl compounds, thus generating more polar metabolites that can be easily excreted. CYP1B1 is also known for its ability to activate procarcinogens into carcinogens. For example, it can hydroxylate 17β-estradiol (E2) into 4-...
Article
Full-text available
In the fight against androgen-sensitive prostate cancer, the enzyme 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is an attractive therapeutic target considering its key role in the formation of androgenic steroids. In this study, we attempted to assess the in vivo efficacy of the compound RM-532-105, an androsterone derivative developed as an...
Article
17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a major player in human endocrinology, being one of the most important enzymes involved in testosterone production. To capitalize on the discovery of RM-532-105, a steroidal 17β-HSD3 inhibitor, we explored the effect of its backbone configuration on inhibitory activity, androgenic profile, and m...
Article
Anticancer structure-activity relationship studies on aminosteroid (5α-androstane) derivatives have emerged with a promising lead candidate: RM-133 (2β-[1-(quinoline-2-carbonyl)pyrrolidine-2-carbonyl]-N-piperazine-5α-androstane-3α,17β-diol), which possesses high in vitro and in vivo activities against several cancer cells, and selectivity over norm...
Article
Two steroids were identified in a supplement named "D-2" following the detection of unknown compounds during the routine testing of an athlete's sample. The main glucuroconjugated metabolites were isolated from this urine by HPLC following enzymatic hydrolysis and identified by GC-MS and NMR analyses as being 2α-hydroxy-5α-androst-3-en-17-one (M1)...
Article
Inhibition of cytochrome P450 1B1 (CYP1B1) represents a promising therapeutic strategy, because it would enable action at three different levels: 1) by inhibiting the formation of mutagenic 4-hydroxy-estradiol, 2) by inhibiting the bioactivation of procarcinogens, and 3) by reducing drug-resistance. Surprisingly, few steroids were reported as inhib...
Article
RM-133 is a key representative of a new family of aminosteroids reported as potent anticancer agents. Although RM-133 produced interesting results in 4 mouse xenograft cancer models when injected subcutaneously, it needs to be improved to increase its in vivo potency. Thus, to obtain an analog of RM-133 with a better drug potential, a structure-act...
Patent
Full-text available
Estrane- based and androstane- based aminosteroid derivs. of formula I [A = C, (substituted) N; B = CO, SO2, CH2, etc.; R1 = OH, halo, alkoxy, acyloxy, etc.; R2 = H, halo, OH, alkoxy, methoxymethoxy, etc.; R3 = H2, O; Z = H, halo, C≡CH, etc.; V = amino acid, etc.; W = CO, SO2, CONH, etc.; X = alkyl, alkoxy, alkylthio, aryl, aryloxy, cycloalkyl, het...
Article
Full-text available
New Cu(II), Pd(II) and Pt(II) complexes, (Cu(L)(H₂O)₂(OAc)) (1), (Cu(HL)(H₂O)₂(SO₄)) (2), (Cu(L)(H₂O)₂(NO₃)) (3), (Cu(L)(H₂O)₂(ClO₄)) (4), (Cu(L)₂(H₂O)₂) (5), (Pd(L)(OAc))H₂O (6), and (Pt(L)₂) (7) were synthesized from 8-ethyl-2-hydroxytricyclo(7.3.1.0(2,7))tridecan-13-one thiosemicarbazone (HL). The ligand and its metal complexes were characterize...
Article
Steroid sulfatase (STS), the enzyme which converts inactive sulfated steroid precursors into active hormones, is a promising therapeutic target for the treatment of estrogen-sensitive breast cancer. We report herein the synthesis and in vitro study of dual-action STS inhibitors with selective estrogen-receptor modulator (SERM) effects. A library of...
Conference Paper
We have reported the dual function of the reductive 17beta-hydroxysteroid dehydrogenases (reductive 17beta-HSDs) in ENDO 2014. Now we have carried out more systematic study in cancer cell biology and animal assay of MCF7 cell induced xenograft tumor in nude mice. We first demonstrated the estrogen synthesis and androgen inactivation activities of...
Article
The steroidogenic enzyme 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is a therapeutic target in the management of androgen-sensitive diseases such as prostate cancer and benign prostate hyperplasia. In this paper, we designed and synthesized the first fluorescent inhibitor of this enzyme by combining a fluorogenic dansyl moiety to the chemic...
Article
Full-text available
Ovarian and pancreatic cancers are two of the most aggressive and lethal cancers, whose management faces only limited therapeutic options. Typically, these tumors spread insidiously accompanied first with atypical symptoms, and usually shift to a drug resistance phenotype with the current pharmaceutical armamentarium. Thus, the development of new d...