Hanh Dufat - Academia.edu (original) (raw)
Papers by Hanh Dufat
CHEMICAL & PHARMACEUTICAL BULLETIN, 1989
Oncology research, 2003
The novel 6-dialkylaminoalkylamino-3,3,12-trimethyl-3,12-dihydro-7H-pyrano[2,3-c]acridine-7-ones ... more The novel 6-dialkylaminoalkylamino-3,3,12-trimethyl-3,12-dihydro-7H-pyrano[2,3-c]acridine-7-ones 5-11 and their benzo [b]pyrano[2,3-h]acridine-7-one counterparts 12-18 were prepared by treatment of acronycine (1) or benzo[b]acronycine (4) with an excess of the appropriate dialkylaminoalkylamine. In both series, the introduction of a dialkylaminoalkylamino side chain at position 6 resulted in a significant increase of the cytotoxic activity against L1210 cells when compared with the parent compounds bearing a methoxy group, accompanied with an increased potency to arrest cells in the G2 + M phases of the cell cycle.
The project ‘AlyPOTEC’ aims to improve the citizen security with respect to counterfeit, falsifie... more The project ‘AlyPOTEC’ aims to improve the citizen security with respect to counterfeit, falsified or poor quality pharmaceutical products. Targeted applications of the project are typically: customs controls, quality control or product authentication by pharmaceutical industrial, or by official medicine control laboratories. The objective of the project is to carry out a comprehensive analysis of these products. A study of the detection capabilities of the THz spectroscopy towards selected samples and counterfeiting criteria will be performed. In fact, this technique could provide a complementary analysis, which will give further information on the counterfeit product origin and “history” (manufacturing process, composition, transport and storage). Comparative analysis with established methods will be achieved to highlight THz technology assets. An innovative, compact and mobile prototype will be developed using fiber coupled components according to the results of the product analy...
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics
The novel 6-dialkylaminoalkylamino-3,3,12-trimethyl-3,12-dihydro-7H-pyrano[2,3-c]acridine-7-ones ... more The novel 6-dialkylaminoalkylamino-3,3,12-trimethyl-3,12-dihydro-7H-pyrano[2,3-c]acridine-7-ones 5-11 and their benzo [b]pyrano[2,3-h]acridine-7-one counterparts 12-18 were prepared by treatment of acronycine (1) or benzo[b]acronycine (4) with an excess of the appropriate dialkylaminoalkylamine. In both series, the introduction of a dialkylaminoalkylamino side chain at position 6 resulted in a significant increase of the cytotoxic activity against L1210 cells when compared with the parent compounds bearing a methoxy group, accompanied with an increased potency to arrest cells in the G2 + M phases of the cell cycle.
Anti-cancer drug design
New prodrugs consisting of a beta-D-glucuronic acid linked to a MDR reversal agent (verapamil, qu... more New prodrugs consisting of a beta-D-glucuronic acid linked to a MDR reversal agent (verapamil, quinine or dipyridamole) through a self-immolative spacer were synthesized. Four of them were selected for their reduced cytoxicity and beta-glucuronidase enzymatic efficient hydrolysis. Combined use of these prodrugs with a beta-D-glucuronyl-spacer-doxorubicin (HMR1826) according to an ADEPT strategy restored in vitro the sensibility of a MDR resistant strain.
Anti-cancer drug design, 1998
The three new hydrophilic prodrugs 2, 3 and 4 have been prepared from methyl (4-hydroxymethyl-2-n... more The three new hydrophilic prodrugs 2, 3 and 4 have been prepared from methyl (4-hydroxymethyl-2-nitrophenyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosid)uronate (5) and doxorubicin. Their low cytotoxicity, efficient release of doxorubicin after hydrolysis by beta-D-glucuronidase, and in the cases of 2 and 3 stability at pH 7.2 fulfil the preliminary requirement for their use in antibody-directed enzyme prodrug therapy or prodrug monotherapy.
ChemInform, 2010
New Friedelane Triterpenoids with Antimicrobial Activity from the Stems of Drypetes paxii. -Two n... more New Friedelane Triterpenoids with Antimicrobial Activity from the Stems of Drypetes paxii. -Two new friedelane-type triterpenes (I) and (II) are isolated together with several known compounds from the stem of the title plant. The isolated natural materials are tested for their antimicrobial activity against some Gram-positive and Gram-negative bacteria and they are found to be modestly active. -(CHIOZEM, D. D.; TRINH-VAN-DUFAT, H.; WANSI, J. D.; DJAMA, C. M.; FANNANG, V. S.; SEGUIN, E.; TILLEQUIN, F.; WANDJI*, J.; Chem.
Zeitschrift für Naturforschung C, 2002
Zanthoxylum scandens, Alkaloids, Phenylpropanoids, (E)-O-Geranylconyferyl Alcohol (9Z, 12Z)-linol... more Zanthoxylum scandens, Alkaloids, Phenylpropanoids, (E)-O-Geranylconyferyl Alcohol (9Z, 12Z)-linoleate
ChemInform, 2009
New Triterpenoids from the Stem Barks of Drypetes tessmanniana. -Isolation and structure elucidat... more New Triterpenoids from the Stem Barks of Drypetes tessmanniana. -Isolation and structure elucidation of the triterpene derivatives (I) and (II) are described. -(DONGFACK, M. D. J.; VAN-DUFAT, H. T.; LALLEMAND, M.-C.; WANSI, J.-D.; SEGUIN, E.; TILLEQUIN, F.; WANDJI*, J.; Chem. Pharm. Bull. 56 (2008) 9, 1321-1323; Dep. Org. Chem., Univ. Yaounde, Yaounde, Cameroon; Eng.) -H. Haber
Biochemical Systematics and Ecology, 2014
ABSTRACT •The first phytochemical study of Miliusa umpangensis.•Miliusanes are chemotaxonomic mar... more ABSTRACT •The first phytochemical study of Miliusa umpangensis.•Miliusanes are chemotaxonomic marker of the genus Miliusa.•Flavonoids with a 1,2,3,5-tetraoxygenated aromatic ring are also characteristic of the genus Miliusa.•Some flavonoids show antiherptic activity.
Tetrahedron Letters, 2013
ABSTRACT Seven new neolignans and a new lignan were isolated from the leaves and the stems of Mil... more ABSTRACT Seven new neolignans and a new lignan were isolated from the leaves and the stems of Miliusa fragrans, along with nine known polyphenolic compounds. Their structures were established through analysis of spectroscopic data, including 1H and 13C NMR, COSY, NOESY, HSQC, HMBC, and HRMS. The isolates were also evaluated for their inhibitory activity against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and their cytotoxicity against KB, MCF7, and NCI-H187 cancer cells.
Tetrahedron, 2004
The key structural feature of Ergot alkaloids, exemplified by lysergic acid 1, is a tetracyclic e... more The key structural feature of Ergot alkaloids, exemplified by lysergic acid 1, is a tetracyclic ergoline ring system. In addition to tetracyclic derivatives, a number of tricyclic analogues were the D ring is open are also found in nature. The representatives of secoergoline group, such as ...
Phytochemistry, 2009
The air-dried stems and ripe fruit of Drypetes inaequalis Hutch. (Euphorbiaceae) were studied. Fo... more The air-dried stems and ripe fruit of Drypetes inaequalis Hutch. (Euphorbiaceae) were studied. Four triterpene derivatives, characterized as lup-20(29)-en-3b,6a-diol, 3b-acetoxylup-20(29)-en-6a-ol, 3b-caffeoyloxylup-20(29)-en-6a-ol and 28-b D-glucopyranosyl-30-methyl 3b-hydroxyolean-12-en-28,30-dioate along with 10 known compounds were isolated from the whole stems. One triterpene, characterized as 3a-hydroxyfriedelan-25-al along with six known compounds were isolated from the ripe fruit. Their structures were established on the basis of spectroscopic analysis and chemical evidence. The triterpenes were tested for antimicrobial activity against some Gram-positive and Gram-negative bacteria, and two of them appeared to be modestly active.
Natural Product Research, 2013
A new pentacyclic triterpenoid and three new derivatives based on the taraxer-14-ene skeleton wit... more A new pentacyclic triterpenoid and three new derivatives based on the taraxer-14-ene skeleton with a C-28 attached a carboxylic acid group have been isolated from the stem bark of Hypodaphnis zenkeri, together with six known compounds. The new product was identified as 2α,3α-dihydroxytaraxer-14-en-28-oic acid (1). Its derivatives, 2α,3α-diacetyltaraxer-14-en-28-oic acid (2), 2α,3α-di-O-carbonyl-2α,3α-dihydroxytaraxer-14-en-28-oic acid (3) and 2α,3α-dipropionyltaraxer-14-en-28-oic acid (4) were obtained by semisynthesis. The known compounds were identified as 3β-hydroxytaraxer-14-en-28-oic acid or aleuritolic acid (5) (McPhail, A.T., McPhail, D.R., Wani, M.C., Wall, M.E. & A.W., Nicholas, A.W. (1989). Identity of maprounic acid with aleuritolic acid. Revision of the structure of maprounic acid: X-ray crystal structure of p-bromobenzyl acetylmaprounate. Journal Natural Products, 52, 212), 3α-hydroxytaraxer-14-en-28-oic acid or isoaleuritolic acid (6), 3α-acetyltaraxer-14-en-28-oic acid acetate or aleuritolic acid acetate (7) (Chaudhuri, S.K., Fullas, F., Brown, D.M., Wani, M.C., Wall, M.E., Cai, L., … Kinghorn, A.D. (1995). Isolation and structural elucidation of pentacyclic triterpenoids from Maprounea africana. Journal of Natural Products, 58, 1-9), 3-oxo-taraxer-14-ene or taraxerone (8) β-sitosterol (9) and stigmasterol (10) (Kamboj & Saluja, 2011), together with fatty acids. Their structures were established on the basis of spectroscopic studies and chemical transformations.
Journal of Medicinal Chemistry, 2006
Twenty-two derivatives belonging to the cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tet... more Twenty-two derivatives belonging to the cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[a]pyrano[3,2-h]acridin-7-one series were synthesized in nine steps starting from 3,5-dimethoxyacetanilide (5) and 2-methoxy-1-naphthalenecarboxylic acid (7). Most of them exhibited submicromolar cytotoxicity when tested against murine leukemia (L1210) and human epidermoid carcinoma (KB-3-1) cell lines. The cytotoxic activity correlated strongly with the ability of the compounds to form covalent adducts with purified DNA. Among the most active compounds, 25, with IC50 values of 0.7 and 0.15 microM against L1210 and KB-3-1, respectively, was selected for evaluation in vivo against Colon 38 adenocarcinoma implanted in mice. This compound was active at 3 mg/kg i.v. (day 12 and 24) with 3/7 tumor free mice by day 80.
CHEMICAL & PHARMACEUTICAL BULLETIN, 1989
Oncology research, 2003
The novel 6-dialkylaminoalkylamino-3,3,12-trimethyl-3,12-dihydro-7H-pyrano[2,3-c]acridine-7-ones ... more The novel 6-dialkylaminoalkylamino-3,3,12-trimethyl-3,12-dihydro-7H-pyrano[2,3-c]acridine-7-ones 5-11 and their benzo [b]pyrano[2,3-h]acridine-7-one counterparts 12-18 were prepared by treatment of acronycine (1) or benzo[b]acronycine (4) with an excess of the appropriate dialkylaminoalkylamine. In both series, the introduction of a dialkylaminoalkylamino side chain at position 6 resulted in a significant increase of the cytotoxic activity against L1210 cells when compared with the parent compounds bearing a methoxy group, accompanied with an increased potency to arrest cells in the G2 + M phases of the cell cycle.
The project ‘AlyPOTEC’ aims to improve the citizen security with respect to counterfeit, falsifie... more The project ‘AlyPOTEC’ aims to improve the citizen security with respect to counterfeit, falsified or poor quality pharmaceutical products. Targeted applications of the project are typically: customs controls, quality control or product authentication by pharmaceutical industrial, or by official medicine control laboratories. The objective of the project is to carry out a comprehensive analysis of these products. A study of the detection capabilities of the THz spectroscopy towards selected samples and counterfeiting criteria will be performed. In fact, this technique could provide a complementary analysis, which will give further information on the counterfeit product origin and “history” (manufacturing process, composition, transport and storage). Comparative analysis with established methods will be achieved to highlight THz technology assets. An innovative, compact and mobile prototype will be developed using fiber coupled components according to the results of the product analy...
Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics
The novel 6-dialkylaminoalkylamino-3,3,12-trimethyl-3,12-dihydro-7H-pyrano[2,3-c]acridine-7-ones ... more The novel 6-dialkylaminoalkylamino-3,3,12-trimethyl-3,12-dihydro-7H-pyrano[2,3-c]acridine-7-ones 5-11 and their benzo [b]pyrano[2,3-h]acridine-7-one counterparts 12-18 were prepared by treatment of acronycine (1) or benzo[b]acronycine (4) with an excess of the appropriate dialkylaminoalkylamine. In both series, the introduction of a dialkylaminoalkylamino side chain at position 6 resulted in a significant increase of the cytotoxic activity against L1210 cells when compared with the parent compounds bearing a methoxy group, accompanied with an increased potency to arrest cells in the G2 + M phases of the cell cycle.
Anti-cancer drug design
New prodrugs consisting of a beta-D-glucuronic acid linked to a MDR reversal agent (verapamil, qu... more New prodrugs consisting of a beta-D-glucuronic acid linked to a MDR reversal agent (verapamil, quinine or dipyridamole) through a self-immolative spacer were synthesized. Four of them were selected for their reduced cytoxicity and beta-glucuronidase enzymatic efficient hydrolysis. Combined use of these prodrugs with a beta-D-glucuronyl-spacer-doxorubicin (HMR1826) according to an ADEPT strategy restored in vitro the sensibility of a MDR resistant strain.
Anti-cancer drug design, 1998
The three new hydrophilic prodrugs 2, 3 and 4 have been prepared from methyl (4-hydroxymethyl-2-n... more The three new hydrophilic prodrugs 2, 3 and 4 have been prepared from methyl (4-hydroxymethyl-2-nitrophenyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosid)uronate (5) and doxorubicin. Their low cytotoxicity, efficient release of doxorubicin after hydrolysis by beta-D-glucuronidase, and in the cases of 2 and 3 stability at pH 7.2 fulfil the preliminary requirement for their use in antibody-directed enzyme prodrug therapy or prodrug monotherapy.
ChemInform, 2010
New Friedelane Triterpenoids with Antimicrobial Activity from the Stems of Drypetes paxii. -Two n... more New Friedelane Triterpenoids with Antimicrobial Activity from the Stems of Drypetes paxii. -Two new friedelane-type triterpenes (I) and (II) are isolated together with several known compounds from the stem of the title plant. The isolated natural materials are tested for their antimicrobial activity against some Gram-positive and Gram-negative bacteria and they are found to be modestly active. -(CHIOZEM, D. D.; TRINH-VAN-DUFAT, H.; WANSI, J. D.; DJAMA, C. M.; FANNANG, V. S.; SEGUIN, E.; TILLEQUIN, F.; WANDJI*, J.; Chem.
Zeitschrift für Naturforschung C, 2002
Zanthoxylum scandens, Alkaloids, Phenylpropanoids, (E)-O-Geranylconyferyl Alcohol (9Z, 12Z)-linol... more Zanthoxylum scandens, Alkaloids, Phenylpropanoids, (E)-O-Geranylconyferyl Alcohol (9Z, 12Z)-linoleate
ChemInform, 2009
New Triterpenoids from the Stem Barks of Drypetes tessmanniana. -Isolation and structure elucidat... more New Triterpenoids from the Stem Barks of Drypetes tessmanniana. -Isolation and structure elucidation of the triterpene derivatives (I) and (II) are described. -(DONGFACK, M. D. J.; VAN-DUFAT, H. T.; LALLEMAND, M.-C.; WANSI, J.-D.; SEGUIN, E.; TILLEQUIN, F.; WANDJI*, J.; Chem. Pharm. Bull. 56 (2008) 9, 1321-1323; Dep. Org. Chem., Univ. Yaounde, Yaounde, Cameroon; Eng.) -H. Haber
Biochemical Systematics and Ecology, 2014
ABSTRACT •The first phytochemical study of Miliusa umpangensis.•Miliusanes are chemotaxonomic mar... more ABSTRACT •The first phytochemical study of Miliusa umpangensis.•Miliusanes are chemotaxonomic marker of the genus Miliusa.•Flavonoids with a 1,2,3,5-tetraoxygenated aromatic ring are also characteristic of the genus Miliusa.•Some flavonoids show antiherptic activity.
Tetrahedron Letters, 2013
ABSTRACT Seven new neolignans and a new lignan were isolated from the leaves and the stems of Mil... more ABSTRACT Seven new neolignans and a new lignan were isolated from the leaves and the stems of Miliusa fragrans, along with nine known polyphenolic compounds. Their structures were established through analysis of spectroscopic data, including 1H and 13C NMR, COSY, NOESY, HSQC, HMBC, and HRMS. The isolates were also evaluated for their inhibitory activity against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) and their cytotoxicity against KB, MCF7, and NCI-H187 cancer cells.
Tetrahedron, 2004
The key structural feature of Ergot alkaloids, exemplified by lysergic acid 1, is a tetracyclic e... more The key structural feature of Ergot alkaloids, exemplified by lysergic acid 1, is a tetracyclic ergoline ring system. In addition to tetracyclic derivatives, a number of tricyclic analogues were the D ring is open are also found in nature. The representatives of secoergoline group, such as ...
Phytochemistry, 2009
The air-dried stems and ripe fruit of Drypetes inaequalis Hutch. (Euphorbiaceae) were studied. Fo... more The air-dried stems and ripe fruit of Drypetes inaequalis Hutch. (Euphorbiaceae) were studied. Four triterpene derivatives, characterized as lup-20(29)-en-3b,6a-diol, 3b-acetoxylup-20(29)-en-6a-ol, 3b-caffeoyloxylup-20(29)-en-6a-ol and 28-b D-glucopyranosyl-30-methyl 3b-hydroxyolean-12-en-28,30-dioate along with 10 known compounds were isolated from the whole stems. One triterpene, characterized as 3a-hydroxyfriedelan-25-al along with six known compounds were isolated from the ripe fruit. Their structures were established on the basis of spectroscopic analysis and chemical evidence. The triterpenes were tested for antimicrobial activity against some Gram-positive and Gram-negative bacteria, and two of them appeared to be modestly active.
Natural Product Research, 2013
A new pentacyclic triterpenoid and three new derivatives based on the taraxer-14-ene skeleton wit... more A new pentacyclic triterpenoid and three new derivatives based on the taraxer-14-ene skeleton with a C-28 attached a carboxylic acid group have been isolated from the stem bark of Hypodaphnis zenkeri, together with six known compounds. The new product was identified as 2α,3α-dihydroxytaraxer-14-en-28-oic acid (1). Its derivatives, 2α,3α-diacetyltaraxer-14-en-28-oic acid (2), 2α,3α-di-O-carbonyl-2α,3α-dihydroxytaraxer-14-en-28-oic acid (3) and 2α,3α-dipropionyltaraxer-14-en-28-oic acid (4) were obtained by semisynthesis. The known compounds were identified as 3β-hydroxytaraxer-14-en-28-oic acid or aleuritolic acid (5) (McPhail, A.T., McPhail, D.R., Wani, M.C., Wall, M.E. & A.W., Nicholas, A.W. (1989). Identity of maprounic acid with aleuritolic acid. Revision of the structure of maprounic acid: X-ray crystal structure of p-bromobenzyl acetylmaprounate. Journal Natural Products, 52, 212), 3α-hydroxytaraxer-14-en-28-oic acid or isoaleuritolic acid (6), 3α-acetyltaraxer-14-en-28-oic acid acetate or aleuritolic acid acetate (7) (Chaudhuri, S.K., Fullas, F., Brown, D.M., Wani, M.C., Wall, M.E., Cai, L., … Kinghorn, A.D. (1995). Isolation and structural elucidation of pentacyclic triterpenoids from Maprounea africana. Journal of Natural Products, 58, 1-9), 3-oxo-taraxer-14-ene or taraxerone (8) β-sitosterol (9) and stigmasterol (10) (Kamboj & Saluja, 2011), together with fatty acids. Their structures were established on the basis of spectroscopic studies and chemical transformations.
Journal of Medicinal Chemistry, 2006
Twenty-two derivatives belonging to the cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tet... more Twenty-two derivatives belonging to the cis-1,2-diacyloxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[a]pyrano[3,2-h]acridin-7-one series were synthesized in nine steps starting from 3,5-dimethoxyacetanilide (5) and 2-methoxy-1-naphthalenecarboxylic acid (7). Most of them exhibited submicromolar cytotoxicity when tested against murine leukemia (L1210) and human epidermoid carcinoma (KB-3-1) cell lines. The cytotoxic activity correlated strongly with the ability of the compounds to form covalent adducts with purified DNA. Among the most active compounds, 25, with IC50 values of 0.7 and 0.15 microM against L1210 and KB-3-1, respectively, was selected for evaluation in vivo against Colon 38 adenocarcinoma implanted in mice. This compound was active at 3 mg/kg i.v. (day 12 and 24) with 3/7 tumor free mice by day 80.