Picture of Jonathan Dimmock

Jonathan Dimmock Emeritus Professor

Address
Thorvaldson 211

Biography

Dr. Dimmock is a medicinal chemist. He obtained his Ph. D. on the syntheses of candidate narcotic analgesics from the University of London, England and then worked as a research chemist in the industrial sector in the U.K. He joined the faculty of the College of Pharmacy (as it was then) in 1967 and rose to be a full professor in 1976. His teaching was principally devoted to a required course in medicinal chemistry and he initiated an elective on drug design. Much of this latter course was incorporated into a book entitled “An Introduction to Drug Design” which was published in 1997. In 1998 Dr. Dimmock received the University of Saskatchewan Students’ Union Teaching Excellence Award.

In 2002 Dr. Dimmock retired in order to work full time in research principally in conjunction with Dr. Umashankar Das.

Research

The research emphasis of Dr. Dimmock continues to be in the realm of cancer chemotherapy. In practice novel compounds are designed as anticancer drugs which are then synthesised and evaluated for their bioactivity. Specifically the principal group of molecules examined are conjugated unsaturated ketones which have an affinity for thiols and not amino and hydroxyl groups which are found in nucleic acids. An aim is to prepare compounds which demonstrate tumour-selective toxicity which are also effective against multidrug resistant tumours. Use is made of computer software packages which enables the shapes of active and inactive molecules to be compared as well as docking compounds to ascertain the extent of binding of molecules at a binding site of a specific enzyme. The modes of action of bioactive compounds are studied and in particular the effects of the novel compounds on mitochondrial function are noted. X-ray crystallography of representative molecules is undertaken to confirm the proposed structures and to reveal the shapes of molecules.

Other investigations undertaken involved the creation of a number of series of novel anticonvulsants, one of which entered a limited clinical trial. Various antimicrobial and antiparasitical agents have been prepared and a highly effective immunosuppressant was involved in a number of preclinical toxicology experiments.

The supervision or co-supervision of a number of M. Sc. and Ph. D. theses has been accomplished as well as assisting the research of various postdoctoral fellows, Visiting Professors and Visiting Scholars. A number of chapters in books and review articles have also been published. To date these studies have led to approximately 240 refereed articles in a variety of journals along with about 100 Abstracts. In addition Dr. Dimmock has been the external examiner of a number of M. Sc. and Ph. D. theses as well as being a frequent reviewer for manuscripts submitted to various journals.

Publications

238      Y. Santiago-Vazquez, U. Das, A. Varela-Ramirez, S.T. Baca, Y. Ayala-Marin, C. Lema, S. Das, A. Baryyan, J.R. Dimmock, R.J. Aguilera, 2016.  Tumor-selective cytotoxicity of a novel pentadiene analogue on human leukemia/lymphoma cells, Clinical Cancer Drugs, 3(2), 138-146.

237      M. Hossain, U. Das, N. Umemura, H. Sakagami, J. Balzarini, E. De Clercq, M. Kawase, J.R. Dimmock, 2016.  Tumor-specific cytotoxicity and structure-activity relationships of novel 1-[3-(2-methoxyethylthio)propionyl]-3,5-bis(benzylidene)-4-piperidones, Bioorganic and Medicinal Chemistry, 24, 2206-2214.

236      A.K. Panda, U. Das, P.K. Roayapalley, H. Sakagami, M. Kawase, J. Balzarini, E. De Clercq and J.R. Dimmock, 2016.  Niacin esters of chalcones with tumour-selective properties, Journal of Enzyme Inhibition and Medicinal Chemistry, 31(6), 1451-1456 

235      U. Das, H.N. Pati, Z. Baráth, Á. Csonka, J. Molnár, J.R. Dimmock, 2016.  1-[3-(2-Hydroxyethylsulfanyl)propanoyl]-3,5-bis(benzylidene)-4-piperidones: A novel cluster of P-glycoprotein dependent multidrug resistance modulators, Bioorganic & Medicinal Chemistry Letters, 26(4), 1319-1321.

234      S.S. Karki, U. Das, N. Umemura, H. Sakagami, S. Iwamoto, M. Kawase, J. Balzarini, E. De Clercq, S.G. Dimmock and J.R. Dimmock, 2016.  3,5-Bis(3-alkylaminomethyl-4-hydroxybenzylidene)-4-piperidones: A Novel Class of Potent Tumor-Selective Cytotoxins, Journal of Medicinal Chemistry, 59, 763-769.

233      E. Robles-Escajeda, U. Das, N.M. Ortega, K. Parra, G. Francia, J.R. Dimmock, A. Varela-Ramirez, R.J. Aguilera, 2016.  A novel curcumin-like dienone induces apoptosis in triple-negative breast cancer cells, Cellular Oncology, 39, 265-277.

232      H. Awad, U. Das, J. Dimmock and A. El-Aneed, 2015.  Establishment of tandem mass spectrometric fingerprint of novel antineoplastic curcumin analogues using electrospray ionization, Rapid Communications in Mass Spectrometry, 29, 1307-1316.

231      L.M. Nunes, M. Hossain, A. Varela-Ramirez, U. Das, Y.M. Ayala-Marin, J.R. Dimmock, R.J. Aguilera, 2016.  A novel class of piperidones exhibit potent, selective and pro-apopotic anti-leukemia properties, Oncology Letters, 11(6), 3842-3848.

230      M.A. Vasquez, E. Iniguez, U. Das, S.M. Beverley, L.J. Herrera, J.R. Dimmock, R.A. Maldonado, 2015.  Evaluation of α-β-Unsaturated Ketones as Antileishmanial Agents, Antimicrobial Agents and Chemotherapy, 59(6), 3598-3601.

229      N. Edraki, U. Das, B. Hemateenejad, J.R. Dimmock, R. Miri, 2016.  Comparative QSAR analysis of 3,5-bis(arylidene)-4-piperidone derivatives: the development of predictive cytotoxicity models, Iranian Journal of Pharmaceutical Research, 15(2), 425-437.

228      R.K. Sharma, S. Kumar, A. Parameswaran and J.R. Dimmock, 2014.  Regulation of N-myristoyltransferase by the Calpain and Caspase Systems, Indian Journal of Biochemistry and Biophysics, 51, 506-511.

227      M. Poorghorban, U. Das, O. Alaidi, J.M. Chitanda, D. Michel, J. Dimmock, R. Verrall, P. Grochulski and I. Badea, 2015.  Characterization of the Host-guest Complex of a Curcumin Analog with β-cyclodextrin and β-cyclodextrin-gemini Surfactant and Evaluation of its Anticancer Activity, International Journal of Nanomedicine, 10, 1-13.

226      R.S.P. Singh, D. Michel, U. Das, J.R. Dimmock and J. Alcorn, 2014.  Cytotoxic 1,5-diaryl-3-oxo-1,5-pentadienes:  An Assessment and Comparison of Membrane Permeability using Caco-2 and MDCK Monolayers, Bioorg. Med. Chem. Lett., 24, 5199-5202.

225      H. Awad, M.J. Stoudemayer, L. Usher, I.J. Amster, A. Cohen, U. Das, R.M. Whitall, J. Dimmock and A. El-Aneed, 2014.  The Unexpected Formation of [M-H]+  Species during MALDI and Dopant-free APPJ MS Analysis of Novel Antineoplastic Curcumin Analogues, J. Mass. Spectrom., 49, 1139-1147.

224      L.N. Nunes, E. Robles-Escajeda, Y. Santiago-Vazquez, N.M. Ortega, C. Lema, A. Muro, G. Almodovar, U. Das, S. Das, J.R. Dimmock, R.J. Aguilera and A. Varela-Ramirez,  2014.  The Gender of Cell Lines Matters when Screening for Novel Anti-cancer Drugs, AAPS Journal, 16, 872-874.

223      U. Das, T. Lorand, S.G. Dimmock, P. Perjesi and J.R. Dimmock, 2015.  3-Benzylidene-4-chromanones:  A Novel Cluster of Anti-tubercular Agents, Journal of Enzyme Inhibition and Medicinal Chemistry, 30(2), 259-263. 

222      Y. Santiago-Vazquez, S. Das, U. Das, E.  Robles-Escajeda, N.M. Ortega, C. Lema, A. Varela-Ramírez, R.J. Aguilera, J. Balzarini, E. De Clercq, S.G. Dimock, D.K.J. Gorecki and J.R. Dimmock, 2014.  Novel 3,5-bis(arylidene)-4-oxo-1-piperidinyl Dimers:     Structure-activity Relationships and Potent Antileukemic and Antilymphoma Cytotoxicity, European Journal of Medicinal Chemistry, 77, 315-322.

213      A.K.Panda, U. Das, J.W. Quail and J.R. Dimmock, 2014.  Synthesis of Bicyclic N-methylpyrazoline and Pyrazole Derivatives from α,β-unsatured Ketones and N,N-dimethylhydrazine:  An Illustration of Reductive Cyclization, Journal of Heterocyclic Chemistry, 51, 219-223.

Patents

R.A. Maldonado, M.A. Vasquez, J.R. Dimmock and U. Das, 2014.  Antiparasitic Effect of bis[3,5-bis-Benzylidene)-4-oxo-1-piperidinyl]amide Derivatives, US Patent Application 61978346.  Filed April 11, 2014.

U. Das and J.R. Dimmock, 2013.  4-Piperidone derivatives as antineoplastics.  United States Provisional Patent Application No. 61/818,080.  Filed May 1, 2013.

J. R. Dimmock and U. Das, 2009. Antineoplastic compounds. PCT Int. Appl. WO 2007059613 A1, May 31/2007. US 7582655, Sep 01/2009.

J.R. Dimmock and E.K. Manavathu, 2000.  Mannich Bases of Conjugated Styryl Ketones.  Granted as U.S. Patent 6,017,933 on January 25.

J.R. Dimmock, 1995.  Semicarbazones Having CNS Activity and Pharmaceutical Preparations Containing Same. Filed in the United States Patent Office, under Serial No. 08/475,313, June 7.  Granted as US Patent 5,741,818 on April 21, 1998.

Funding

Grants have been obtained from the Canadian Institutes of Health Research and its predecessor the Medical Research Council of Canada. Other sources of funding are Mitacs Accelerate. the Industrial Liaison Office of the University of Saskatchewan, the Maunders McNeil Foundation Inc. and a number of pharmaceutical companies. In addition Dr. Dimmock was a co-applicant in the successful funding for establishing the Saskatchewan Structural Sciences Centre.