MyKnowledgeTransfer

Guanrui Pan, Hei-Tak Tse, Ho-Wai Chan, and Wan Chan* (2024)

"Using 2-(2-Chlorophenyl)thiazolidine-4-carboxylic Acid as a Novel Biomarker for 2-Chlorobenzalmalononitrile Exposure", Chemical Research in Toxicology 2024, XXX, XXX-XXX.

Chemical Research in Toxicology => Impact Factor 4.10 (as in 2022)

... the development of a novel biomarker for 2-chlorobenzalmalononitrile (CS) gas exposure. Using liquid chromatographic and mass spectrometric techniques, we found that CS underwent rapid hydrolysis into 2-chlorobenzaldehyde (2-CBA), a highly reactive intermediate that reacted swiftly with endogenous cysteine (Cys) and Cys residues in proteins...

Chemical Research in Toxicology 2024, XX, X, XXX-XXX. ABSTRACT

Yat-Hing Ham, Guanrui Pan, Ho Wai Chan, and Wan Chan* (2022)

"LC-MS/MS Quantitation of Formaldehyde–Glutathione Conjugates as Biomarkers of Formaldehyde Exposure and Exposure-Induced Antioxidants: A New Look on an Old Topic", Chemical Research in Toxicology 2022, 35(5), pp 858-866.

Chemical Research in Toxicology => Impact Factor 4.10 (as in 2022)

... data showed that these exposure-induced adducts exhibited good antioxidative properties, which can protect cells from hydrogen peroxide mediated oxidative insult...

Chemical Research in Toxicology 2022, 35, 5, 858-866. ABSTRACT

Guanrui Pan, Yat-Hing Ham, Ho-Wai Chan, Jing Yao*, and Wan Chan* (2020)

"LC-MS/MS Coupled with a Stable-Isotope Dilution Method for the Quantitation of Thioproline-Glycine: A Novel Metabolite in Formaldehyde- and Oxidative Stress-Exposed Cells", Chemical Research in Toxicology 2020, 33(7), pp 1989-1996.

Chemical Research in Toxicology => Impact Factor 3.739 (in 2020)

...a variety of GSH-derived thiazolidine metabolites may serve as potential biomarkers for formaldehyde exposure...

Chemical Research in Toxicology 2020, 2020, 33, 7, 1989–1996. ABSTRACT

Wan Chan*, Yat-Hing Ham, Long Jin, Ho-Wai Chan, Yee Lam Wong, Chi Kong Chan, and Pui-Yin Chung (2019)

"Quantification of a Novel DNA-Protein Crosslink Product Formed by Reacting Apurinic/Apyrimidinic Sites in DNA with Cysteine Residues in Protein by Liquid Chromatography-Tandem Mass Spectrometry Coupled with the Stable Isotope-Dilution Method", Analytical Chemistry 2019, 91, 8, 4987-4994.

Analytical Chemistry 2019, 91, 8, 4987-4994. ABSTRACT

Analytical Chemistry => Impact Factor 6.986 (in 2020)

Wing Chi Chan, Dennis Ho Wai Chan, Kin Wo Lee, Wing Shan Tin, Ho Ning Wong, Richard K. Haynes* (2018)

"Evaluation and optimization of synthetic routes from dihydroartemisinin to the alkylamino-artemisinins artemiside and artemisone: A test of N-glycosylation methodologies on a lipophilic peroxide", Tetrahedron 2018, 74(38), pp 5156-5171.

Tetrahedron => Impact Factor 2.457 (in 2020)

Tetrahedron 2018, 74(38), pp 5156-5157. ABSTRACT

Weiwei Li, Chi-Kong Chan, Yee-Lam Wong, K.K. Jason Chan, Ho Wai Chan and Wan Chan* (2018)

"Cooking methods employing natural anti-oxidant food additives effectively reduced concentration of nephrotoxic and carcinogenic aristolochic acids in contaminated food grains", Food Chemistry 2018, 264, pp 270-276.

Food Chemistry => Impact Factor 7.514 (in 2020)

... the addition of healthy dietary supplements during cooking is a highly efficient method in lowering the concentration of aristolochic acids ...

Food Chemistry 2018, 264, pp 270-276. ABSTRACT

Yinan Wang, Ho-Wai Chan and Wan Chan* (2016)

"Facile Formation of DNA Adduct of Semicarbazide in Reaction with Apurinic/Apyrimidinic Sites in DNA", Chemical Research in Toxicology 2016, 29(5), pp 834-840.

Chemical Research in Toxicology => Impact Factor 3.739 (in 2020)

... demonstrated for the first time SEM reacts rapidly with apurinic/apyrimidinic sites in an endogenous DNA lesion ...

Chemical Research in Toxicology 2016, 29(5), pp 834-840. ABSTRACT

Yuanjiao Li, Jingjing Liu, Yajie Wang, Ho Wai Chan, Lianrong Wang and Wan Chan* (2015)

"Mass Spectrometric and Spectrophotometric Analyses Reveal an Alternative Structure and a New Formation Mechanism for Melanin", Analytical Chemistry 2015, 87: 15, pp.7958-7963.

Analytical Chemistry => Impact Factor 6.986 (in 2020)

... investigated the formation mechanism and chemical structure of melanin that results from the self-assembly of l-3,4-dihydroxyphenylalanine (l-DOPA) ...

Analytical Chemistry 2015, 87:15, pp.7958-7963. ABSTRACT

Richard K. Haynes*, Kwan-Wing Cheu, Ho-Wai Chan, Ho-Ning Wong, Ka-Yan Li, Maggie Mei-Ki Tang, Min-Jiao Chen, Zu-Feng Guo, Zhi-Hong Guo, Kumar Sinniah, Amanda B. Witte, Dr. Paolo Coghi, Diego Monti (2012)

"Interactions between Artemisinins and other Antimalarial Drugs in Relation to the Cofactor Model – A Unifying Proposal for Drug Action", ChemMedChem 2012, 7: 12, pp.2204-2226.

ChemMedChem => Impact Factor of 3.466 (in 2020)

... The antagonism exerted by 4-aminoquinolines (e.g. piperaquine) and the additivity/synergism exerted by arylmethanols (e.g. quinine) on the antimalarial activities of MB, riboflavin, and artemisinins correlates with the inhibition of oxidation by artemisinins of LMB, reduced flavins by the quinolines, and lack of any effect on the oxidation by arylmethanols; it further allows proposal for a unifying mechanism of action...

ChemMedChem 2012, 7:12, pp.2204-2226. ABSTRACT

Judith H Waknine-Grinberg; Nicholas Hunt; Annael Bentura-Marciano; James A McQuillan; Ho-Wai Chan; Wing-Chi Chan; Yechezkel Barenholz; Richard K Haynes; Jacob Golenser (2010)

"Artemisone effective against murine cerebral malaria", Malaria Journal 2010, 9: 227.

... Artemisone was the most efficient drug tested, and could prevent death even when administered at relatively late stages of cerebral pathogenesis. ...

Malaria Journal, 2010, 9:227 OpenAccess

Haynes, R. K.; Chan, H.-W.; Lung, C. M.; Ng, N. C.; Wong, H. N., Shek, L. Y., Williams, I.D.; Cartwright, A.; Gomes, M. F. (2007)

"Artesunate and Dihydroartemisinin (DHA): Unusual Decomposition Products Formed under Mild Conditions and Comments on the Fitness of DHA as an Antimalarial Drug",ChemMedChem 2007, 2(10), pp. 1448-1463.

ChemMedChem => Impact Factor of 3.466 (in 2020)

... thermal degradation of DHA reveals a thermal lability which would pose a problem not only in relation to ICH stability testing guidelines, but in the use of DHA in fixed formulations currently under development. ...

ChemMedChem 2007 2(10) ABSTRACT

Haynes, R. K.; Fugmann, B.; Stetter, J.; Rieckmann, K.; Heilmann, H.D.; Chan, H.-W.; Cheung, M.-K.; Lam, W.-L.; Wong, H.-N.; Croft, S. L.; Vivas, L.; Rattray, L.; Stewart, L.; Peters, W.; Robinson, B. L.; Edstein, M. D.; Kotecka, B.; Beckermann, B.; Gerisch, M.; Radtke, M.; Schmuck, G.; Steinke, W.; Wollborn, U.; Schmeer, K.; Roemer, A. (2006)

COVER PAGE STORY!!

"Artemisone - A Highly Active Antimalarial Drug of the Artemisinin Class",Angewante Chemie Internatinal Edition 2006, 45, pp. 2082-2088.

Angewante Chemie Internatinal Edition => Impact Factor of 15.336 (in 2020)

...Efficacies of artemisone against the malaria parasite are substantially greater than those of the current artemisinin gold standard ...

Haynes, R. K.; Chan, H.-W.; Ho, W.-Y.; Ko, C. K.-F.; Gerena, L.; Kyle, D. E.; Peters, W.; Robinson, B. L. (2005)

"Convenient Access Both to Highly Antimalaria-Active 10-Arylaminoartemisinins, and to 10-Alkyl Ethers Including Artemether, Arteether, and Artelinate",ChemBioChem 2005, 6(4), pp. 659-667.

ChemBioChem => Impact Factor 3.164 (in 2020)

...an economical phase-transfer method is used to prepare antimalaria-active artemisinin derivatives...

Haynes, R. K.; Ho, W. Y.; Chan, H.-W.; Fugmann, B.; Stetter, J.; Croft, S. L.; Vivas, L.; Peters, W.; Robinson, B. L. (2004)

"Highly Antimalarial-Active Artemisinin Derivatives: Biological Activity does not Correlate with chemical Reactivity",Angew. Chem. Int. Ed. 2004, 43, pp. 1381-1385.

Angewante Chemie Internatinal Edition => Impact Factor of 15.336 (in 2020)

...several antimalaria-active trioxanes cannot obviously generate C-centered radicals......evidence suggests that binding of the artemisinin to a specific target is involved...

Haynes, R. K.; Chan, H.-W.; Cheung, M.-K.; Chung, S.-T.; Lam, W.-L.; Tsang, H.-W.; Voerste, A.; Williams, I. D. (2003)

"Stereoselective Preparation of 10alpha- and 10beta-Aryl Derivatives of Dihydroartemisinin",European J. Org. Chem. 2003, pp. 2098-2114. [Abstract]

Eur J Org Chem => Impact Factor 3.021 (in 2020)

The stereochemistry of the Lewis acid-catalysed arylations, which is common to that observed for the Lewis acid-catalysed arylation of pyranosyl glycosides with axial anomeric leaving groups in general, may be rationalized in terms of axial attack from the Si face of the half-chair oxonium ion intermediate. On the other hand, the Grignard reagents activate the axial bromide to elimination through complexation, and thereby the aryl nucleophile attacks the incipient oxonium ion from the Re face.

Haynes, R. K.; Chan, H.-W.; Cheung, M.-K.; Lam, W.-L.; Soo, M.-K.; Tsang, H.-W.; Voerste, A.; Williams, I. D. (2002)

"C-10 Ester and Ether Derivatives of Dihydroartemisinin-10alpha-Artesunate, Preparation of Authentic 10beta-Artesunate, and of Other Ester and Ether Derivatives Bearing Potential Aromatic Intercalating Groups at C-10",European J. Org. Chem. 2002, pp. 113-132. [Abstract]

Eur J Org Chem => Impact Factor 3.021 (in 2020)

Preparative and stereochemical aspects of reactions providing new C-10 ester and ether derivatives of the antimalarial drug dihydroartemisinin have been examined. beta-Artesunate has been prepared for the first time, and has been differentiated from the antimalarial alpha-artesunate ...... New ester and ether derivatives bearing potential intercalating groups have been synthesised by means of the Schmidt, Mitsunobu and DCC coupling procedures, by acylation in the presence of DMAP, or by hydroxy activation with BF3 as catalyst.

Liu, J.-H.; Chan, H.-W.; Wong, H. N. C. (2000)

"Highly Regioselective Synthesis of 3,4-Disubstituted 1H-Pyrrole",J. Org. Chem. 2000, 65, pp.3274-3283.

J Org Chem => Impact Factor 4.354 (in 2020)

[Abstract]

which reached a citation frequency of 48 (up to Jan 2003), including those by two recent reviews (Hassan, J. et al "Aryl-Aryl Bond Formation One Century after the Discovery of the Ullmann Reaction" Chemical Reviews 2002, 102 pp.1359-1469 & Ferreira, V.F. et al "Recent Advances in the Synthesis of Pyrroles", Organic Preparations and Procedures International 2001, 33 p.411-)

Liu, J.-H.; Chan, H.-W.; Xue, F.; Wang, Q.-G.;Mak, T. C. W. and Wong, H. N. C.  (1999)

"Generation and Trapping Reactions of 1-tert-Butoxycarbonyl-3,4-didehydro-1H-pyrrole",J. Org. Chem. 1999, 64, pp. 1630-1634.

J Org Chem => Impact Factor 4.354 (in 2020)

which is cited by a recent review writen by international experts in hypervalent iodine compounds (Zhdankin, V. V.; Stang, P.J. "Recent Developments in the Chemistry of Polyvalent Iodine Compounds" Chemical Reviews 2002, 102 p.2523-2584 & Wirth, T. et al "Hypervalent Iodine Compounds: Recent Advances in Synthetic Applications" Synthesis-Stuttgart 1999 (8) p.1271-1287)

Chan, H.-W.; Chan, P.-C.; Liu, J.-H. and Wong, H. N. C.  (1997)

"3,4-Bis(trimethylsilyl)-1H-pyrrole: a Versatile Building Block for Unsymmetrically 3,4-Disubstituted Pyrroles", Chem. Commun. 1997,pp. 1515-1516. 

Chem Commun => Impact Factor 6.222 (in 2020)

which is cited by review articles on synthetic methodology of pyrroles (Ferreira, V.F. et al "Recent Advances in the Synthesis of Pyrroles", Organic Preparations and Procedures International 2001, 33 p.411- & Gilchrist, T.L. "Synthesis of Aromatic Heterocycles" Journal of the Chemical Society - Perkin Transactions 1 1999,(20) p.2849-2866).

Jones, R. L.; Qian, Y.-M.; Wong, H. N. C.; Chan, H.-W.; Yim, A. P. C.  (1997)

"Prostanoid Action on the Human Pulmonary Vascular System", Clin. Exp. Pharmacol. Physiol.. 1997, 24(12), pp. 969-972. 

Impact Factor 2.372 (in 2014)

Jones, R. L.; Qian, Y.-M.; Wise, H.; Wong, H.N. C.; Lam, W.-L.; Chan, H.-W.; Yim, A. P. C.; Ho, J. K. S.  (1997)

"Relaxant Actions of Nonprostanoid Prostacyclin Mimetics on Human Pulmonary Artery", J. Cardiovasc. Pharmacol. 1997, 29(4), pp.525-535. 

Impact Factor 2.904 (in 2014)

The First Enlightenments

    I got my B.Sc. in The Chinese University of Hong Kong (香 港 中 文 大 學 ) in the early 90's and decided to further my studies in the field of synthetic organic chemistry in Department of Chemistry in the same university.  Accordingly, having been working on a project related to pharmacology of prostaglandin I₂ mimetics, I worked closely with international experts - Prof. Robert Leslie JONES (who is specialized in prostaglandin pharmacology and is now Emeritus Prof of pharmacologgy in School of Biomedical Sciences, CUHK, and was affiliated with Strathclyde Institute of Pharmacy and Biomedical Sciences) and Prof. Henry Nai Ching WONG (who is specialized in synthetic organic chemistry, development of novel synthetic strategies). 

The Story of Prostacyclin Receptor

    Prostaglandin I₂ (also known as PGI₂ or prostacyclin) is a naturally-occurring substance produced inside our body.  The natural receptor responding to this substance is called prostacyclin receptor or IP-receptor.  The natural agonist 'prostacyclin' is best known for its ability to prevent the clumping of blood platelets and to increase blood flow through tissues. However, it is also a powerful stimulant of sensory nerve endings. Released with prostaglandin E₂ at the site of inflammation, it can cause redness, heat, swelling and pain.  Owing to its effect on such a wide variety of pharmacological responses, identification of any achiral IP-receptor agonist, partial agonist or antagonist must have much pharmacological implications.  In-depth investigations on the matter of quantitative structure-activity relationship (QSAR) could allow us to develop more cost-effective cardiovascular pharmaceuticals.

What is an agonist and what is an antagonist?

New Synthetic Strategy in Heterocyclic Chemistry

    Substantially involved in the organic synthesis of potential prostacyclin receptor antagonists (research highlights) using a wide-variety of synthetic strategy and modern synthetic technology, series of targeted achiral heterocyclic compounds have been actualized.  Recently, a partial agonist which is achiral and structurally-different from the prostacyclin has been identified in this study.  In the way to successfully syntheses of targeted molecules, a new synthetic methodology involving the use of organoboroxines, reactive arylsilane and hypervalent iodine compound has been substantially explored.  These years' intensive research experiences rendered me a Ph.D. from The Chinese University of Hong Kong in 1997 (the year Hongkong re-unified to People's Republic of China).

Interaction with Pharmaceutical Industry

Thereafter, I joined in pharmaceutical manufacturing industry.  Do you know what industrial guys want is not only cost-effectiveness, but also efficiency and quality?  The word 'quality' has been the most popular amongst bosses' instructions to his subordinates.  Since the Asia's recent dramatic change in the economic conditions, Hongkong capitalists has realized that attractive prices is no more applicable to all 'Made in Hong Kong' products.  Improving the quality of products by means of quality assurance practices is the ultimate goal of all successful enterpreneurs.  That is, careful investigations along with innovative problem-solving skills is the most demanded quality of an applause-winning technical staff.  In the last decade, various countries have been competing in the modernization of traditional Chinese medicines. Based on Hongkong people's knowledge on traditional Chinese medicines (of course, more than 90% of Hongkongese are Chinese and knows a lot on use of TCM) and our extensive experiences in advanced manufacturing technology, our local pharmaceutical industry certainly gets extra-competativeness even in an international context. In light of this advantage, Department of Health of the Hongkong SAR government has recently imposed a series of standards and regulations in parallel to the upgrades of the quality of local pharmaceutical industries.  This also paved a highway for the furture's rapid modernization of traditional Chinese medicine within the Pearl River Delta area, which is one of the top agendas in the mission of building up Hongkong's Hi-Tech industry. 

  "We (Hong Kong and Shanghai) are just like two engines of an aircraft taking off now in the 21st Century, taking the country into [the role of] an economic super power in the next 10 years or so."   "Shanghai is working with the Yangtze River Basin while Hong Kong is working with the Pearl River Delta. ..... In terms of strength, attainment, growth potential, the Pearl River Delta has always been ahead of Shanghai together with the Yangtze River Basin. And it'll continue to be the case."   "the days of over-dependence on property and asset-priced inflation are behind us. We must concentrate on innovation, technology, logistics and services if we are to compete as a knowledge-based economy."   Chief Secretary for Administration Donald Tsang (The Business Week 11th Annual Asia Leadership Forum, 26-Jun-2002 ) "成 本 高 不 是 問 題 ， 最 重 要 是 回 報 率 ......要 保 持 這 種 優 勢 ， 香 港 必 須 不 斷 提 高 生 產 力 ， 抵 消 高 昂 的 成 本 。 "人 力 資 源 管 理 學 會 外 務 總 監 吳 克 儉 (9-July2002,明報)

The Molecule that Can Help the Third World

Since late 90's, I have been taking part in active research on traditional Chinese medicine in Department of Chemistry, The Hong Kong University of Science & Technology where a programme on development of drugs for fighting malaria. I was involved in the design and synthesis of artemisinin-related antimalarial and antiparasitic agents. Malaria is by far the world's most important tropical parasitic disease, and kills more people than any other communicable disease except tuberculosis. Qinghaosu (also known as artemisinin) was isolated from the Chinese herb qing hao (青 蒿 Artemisia annua).The compound is especially active against multidrug resistant falciparum malaria, and the World Health Organization has a number of programmes aimed at optimizing use of this drug and its derivatives for clinical use against malaria. Activities were under way which include the mapping of the mode of action, the preparation of new derivatives, and evaluation of cytotoxicities against a number of cell lines. In these years I worked with internationally-renowned specialist on malaria and pharmaceutical chemistry: Prof. Richard Kingston HAYNES 韓 利 強 教 授  , who is now in Centre of Excellence for Pharmaceutical Sciences, North-West University, South Africa. He has kept inspiring me by unlimited imagination and kept me updated with invaluable knowledge on the state-of-art technology in modern pharmaceutical development programmes. Since 1995, the German Pharmaceutical giant - Bayer AG started to sponsor our investigations into the development of antimalarial drugs based on our new findings on qinghaosu derivatives. The collaboration between Bayer AG and HKUST further tightened in 1998 onwards - witnessed by the setting-up of the HKUST-Bayer Research Laboratory.   Recently, our research project has been also collaborating with Medicines for Malaria Venture (MMV), which is an independent not-for-profit foundation aiming to develop new, effective and affordable anti-malarial drugs. This encouraging news has been reported in Genesis issued in Nov 2001.