Dr Randolph Arroo

Job: School of Pharmacy Head of Research

Faculty: Health and Life Sciences

School/department: Leicester School of Pharmacy

Research group(s): Chemistry for Health

Address: De Montfort University, The Gateway, Leicester, LE1 9BH

T: +44 (0)116 250 6386

E: rrjarroo@dmu.ac.uk

W: www.dmu.ac.uk/hls

 

Publications and outputs 

 

  • The synthesis of 4,6-diaryl-2-pyridones and their bioactivation in CYP1 expressing breast cancer cells
    The synthesis of 4,6-diaryl-2-pyridones and their bioactivation in CYP1 expressing breast cancer cells Lodhi, Sabahat; Ankrett, Dyan N.; Wilsher, Nicola E.; Potter, Gerard A.; Beresford, Kenneth J. M.; Arroo, R. R. J.; Ruparelia, K. C. As part of a programme to develop anticancer prodrugs which are activated by cytochrome P450 (CYP)1B1, a library of 4,6-diaryl-2-pyridones was synthesised in yields of 6-60% from the corresponding chalcones. A number of these derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing little toxicity towards a non-tumour breast cell line with no CYP expression. Metabolism studies provided evidence supporting the involvement of CYP1 enzymes in the bioactivation of these compounds. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • New resveratrol analogues for potential use in diabetes and cancer.
    New resveratrol analogues for potential use in diabetes and cancer. Zeka, K.; Arroo, R. R. J.; Hasa, Dritan; Beresford, Kenneth J. M.; Ruparelia, K. C. Resveratrol is a well notorious compound that may play a role in the prevention of diabetes complications and different cancers. Along, resveratrol, a naturally occurring phytoalexin, is known to exert numerous beneficial effects in the organism. Isolation of resveratrol from plants, however, has been proved being difficult. Importantly, the bioavailability in the body is poor therefore capability is reduced and not enough resveratrol reaches the target organ. In this study we generated different methoxylated resveratrol analogues using Wittig reaction. Trans stilbene obtained was 0.08 g and the cis one was 0.01 g. Additionally with the Horner-Witting method a yield of 0.15 g trans stilbene was obtained. By substituting the hydroxyl group with methoxy group at different positions on the aromatic rings, we could increase the efficacy and bioavailability of the Trans form of resveratrol. open access journal
  • Chemical properties of thymoquinone, a monoterpene isolated from the seeds of Nigella sativa Linn.
    Chemical properties of thymoquinone, a monoterpene isolated from the seeds of Nigella sativa Linn. Arroo, R. R. J.; Alfa, H.H. Thymoquinone is the main ingredient of the essential oil extracted from the seeds of Nigella sativa L. (Ranunculaceae). The monoterpene is considered to be the active pharmaceutical ingredient in the seeds, which have traditionally been highly prized for their medicinal properties. The compound has been the focus of a considerable number of pharmacological investigations and has been reviewed regularly for its action against a variety of inflammatory diseases, its effect on metabolic syndrome, and its potential anticancer properties. While discussing the chemical and pharmacological properties of thymoquinone, recent reviews have reflected on the keto-enol tautomerism of thymoquinone. Specifically, thymoquinone is described as a tautomeric compound, where the keto-form is said to be the major configuration that is responsible for its pharmacological properties [1, 2]. In both reviews, reference is made to a 2005 review by Salem [3]. The latter review discusses a range of activities of thymoquinone, mainly on cell signalling and antioxidant (scavenging) molecular mediators involved in the process of inflammation. However, no mention is made in this review of keto- or enol forms of thymoquinone. Moreover, the chemical structure of thymoquinone does not allow keto-enol tautomerism. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • Recent advances in chemistry, therapeutic properties and sources of polydatin
    Recent advances in chemistry, therapeutic properties and sources of polydatin Arroo, R. R. J.; Sohretoglu, D.; Yuzbasioglu, B.M.; Kuruuzum-Uz, A. Polydatin (PLD), the 3-O-β-glucopyranoside of the well-known stilbenoid compound resveratrol, is a major compound of Fallopia japonica (Houtt.) R. Decr. (Japanese knotweed), which is widely used in traditional Chinese medicine to treat infection, inflammatory diseases and circulatory problems. It has shown a wide range of biological activities including anti-inflammatory, anti-oxidant, anti-cancer, neuroprotective, hepatoprotective, nephroprotective and immunostimulatory effects. Although resveratrol has similar beneficial effects, its low bioavailability has remained a problem. Glycosylation increases solubility of resveratrol in an aqueous environment, thus improving its bioavailability. This has led to a growing interest in PLD. Promising results obtained from bioactivity studies have boosted an intense research on this compound. The aim of this review is to give a comprehensive overview of the botanical sources, pharmacology, biosynthesis, biotechnological production, and bioactivities of PLD, and to discuss clinical studies on this compound. Joint review by Hacettepe University, Faculty of Pharmacy, Department of Pharmacognosy and De Montfort University, Leicester School of Pharmacy.
  • Tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1–mediated metabolism to the product 4′ hydroxy tangeretin
    Tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1–mediated metabolism to the product 4′ hydroxy tangeretin Surichan, Somchaiya; Arroo, R. R. J.; Tsatsakis, A. M.; Androutsopoulos, V. P. Tangeretin is a polymethoxylated flavone with multifaceted anticancer activity. In the present study, the metabolism and further antiproliferative activity of tangeretin was evaluated in the CYP1 expressing human breast cancer cell lines MCF7 and MDA–MB–468 and the normal breast cell line MCF10A. Tangeretin was converted to 4ʹ OH tangeretin by recombinant CYP1 enzymes and in MCF7 and MDA–MB–468 cells. This metabolite was absent in MCF10A cells that did not express CYP1 enzymes. Tangeretin exhibited submicromolar IC50 (0.25±0.15 μM) in MDA–MB–468 cells, whereas it was less active in MCF7 cells (13.5±0.8 μM) and completely inactive in MCF10A cells (>100 μM). In MDA–MB–468 cells that were coincubated with the CYP1 inhibitor acacetin, an approximately 70–fold increase was noted in the IC50 (18±1.6 μM) of tangeretin. In the presence of the CYP1 inhibitor acacetin, the conversion of tangeretin to 4ʹ OH tangeretin was significantly reduced in MDA–MB–468 cells (2.55±0.19 μM vs. 6.33±0.12 μM). The mechanism of antiproliferative action involved cell cycle arrest at the G1 phase for MCF7 and MDA–MB–468 cells, whereas the cell cycle of MCF10A cells was unaffected by 10 μM of tangeretin treatment for 24 and/or 48 h. Tangeretin was further shown to induce CYP1 enzyme activity and CYP1A1/CYP1B1 protein expression in MCF7 and MDA–MB–468 cells. Taken collectively, the results suggest that tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1–mediated metabolism to the product 4ʹ hydroxy tangeretin. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
  • Investigation of Linum flavum (L.) Hairy Root Cultures for the Production of Anticancer Aryltetralin Lignans.
    Investigation of Linum flavum (L.) Hairy Root Cultures for the Production of Anticancer Aryltetralin Lignans. Arroo, R. R. J.; Hano, C.; Renouard, S.; Corbin, C.; Drouet, S.; Medvedec, B.; Doussot, J.; Colas, C.; Maunit, B.; Bhambra, A. S.; Gontier, E.; Jullian, N.; Mesnard, F.; Boitel, M.; Abbasi, B. H.; Lainé, E. Linum flavum hairy root lines were established from hypocotyl pieces using Agrobacterium rhizogenes strains LBA 9402 and ATCC 15834. Both strains were effective for transformation but induction of hairy root phenotype was more stable with strain ATCC 15834. Whereas similar accumulation patterns were observed in podophyllotoxin-related compounds (6-methoxy-podophyllotoxin, podophyllotoxin and deoxypodophyllotoxin), significant quantitative variations were noted between root lines. The influence of culture medium and various treatments (hormone, elicitation and precursor feeding) were evaluated. The highest accumulation was obtained in Gamborg B5 medium. Treatment with methyl jasmonate, and feeding using ferulic acid increased the accumulation of aryltetralin lignans. These results point to the use of hairy root culture lines of Linum flavum as potential sources for these valuable metabolites as an alternative, or as a complement to Podophyllum collected from wild stands. Collaboration with: Université d’Orléans, 28000 Chartres, France, Université de Picardie Jules Verne, F-80037 Amiens, France De Montfort University Open access article
  • New Hydrogels Enriched with Antioxidants from Saffron Crocus Can Find Applications in Wound Treatment and/or Beautification
    New Hydrogels Enriched with Antioxidants from Saffron Crocus Can Find Applications in Wound Treatment and/or Beautification Zeka, K.; Ruparelia, K. C.; Sansone, C.; Macchiarelli, G.; Continenza, M. A.; Arroo, R. R. J. Saffron extracts have a long history of application as skin protectant, possibly due to their ability to scavenge free radicals. In this work, the performance of a hydrogel enriched with antioxidant compounds isolated from saffron crocus (Crocus sativus L.) petals was tested. These hydrogels could be considered as new drug delivery system. Hydrogels are crosslinked polymer networks that absorb large quantities of water but retain the properties of a solid, thus making ideal dressings for sensitive skin. We tested antioxidant-en- riched hydrogels on primary mouse fibroblasts. Hydrogels enriched with kaempferol and crocin extracted from saffron petals showed good biocompatibility with in vitro cultured fibroblasts. These new types of hydrogels may find applications in wound treatment and/or beautification. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link
  • Nobiletin bioactivation in MDA-MB-468 breast cancer cells by cytochrome P450 CYP1 enzymes.
    Nobiletin bioactivation in MDA-MB-468 breast cancer cells by cytochrome P450 CYP1 enzymes. Surichan, Somchaiya; Arroo, R. R. J.; Ruparelia, K. C.; Tsatsakis, A. M.; Androutsopoulos, V.P. Nobiletin is a fully methoxylated flavone that has demonstrated anticancer activity via multiple modes of action. In the present study, the metabolism and further antiproliferative activity of nobiletin was evaluated in the CYP1 expressing human breast cancer cell line MDA–MB–468 and the normal breast cell line MCF10A. Nobiletin was metabolized in MDA–MB–468 cells to a single-demethylated derivative assigned NP1. This metabolite was absent in MCF10A cells that did not express CYP1 enzymes. Nobiletin exhibited submicromolar IC50 (0.1±0.04 μM) in MDA–MB–468 cells, whereas it was considerably less active in MCF10A cells (40 μM). In the presence of the CYP1 inhibitor acacetin, the conversion of nobiletin to NP1 was significantly reduced in MDA–MB–468 cells. Furthermore, a significant increase was noted in the population of the cells at the G1 phase, following treatment with nobiletin (10 μM) for 24 h compared with the control cells treated with DMSO (0.1%) alone (55.9±0.14 vs. 45.6±1.96), whereas the cell cycle of MCF10A cells was not significantly altered under the same treatment conditions. Taken collectively, the results suggest that nobiletin is selectively bioactivated in MDA–MB–468 breast cancer cells via metabolism by the CYP1 family of enzymes. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link
  • Specialized Plant Metabolism Characteristics and Impact on Target Molecule Biotechnological Production.
    Specialized Plant Metabolism Characteristics and Impact on Target Molecule Biotechnological Production. Matsuura, H.N.; Malik, S.; de Costa, F.; Yousefzadi, M.; Mirjalili, M. H.; Arroo, R. R. J.; Bhambra, Avninder S.; Strnad, M.; Bonfill, M.; Fett-Neto, A.G. Plant secondary metabolism evolved in the context of highly organized and differentiated cells and tissues, featuring massive chemical complexity operating under tight environmental, developmental and genetic control. Biotechnological demand for natural products has been continuously increasing because of their significant value and new applications, mainly as pharmaceuticals. Aseptic production systems of plant secondary metabolites have improved considerably, constituting an attractive tool for increased, stable and large-scale supply of valuable molecules. Surprisingly, to date, only a few examples including taxol, shikonin, berberine and artemisinin have emerged as success cases of commercial production using this strategy. The present review focuses on the main characteristics of plant specialized metabolism and their implications for current strategies used to produce secondary compounds in axenic cultivation systems. The search for consonance between plant secondary metabolism unique features and various in vitro culture systems, including cell, tissue, organ, and engineered cultures, as well as heterologous expression in microbial platforms, is discussed. Data to date strongly suggest that attaining full potential of these biotechnology production strategies requires being able to take advantage of plant specialized metabolism singularities for improved target molecule yields and for bypassing inherent difficulties in its rational manipulation. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link
  • The synthesis of chalcones as anticancer prodrugs and their bioactivation in CYP1 expressing breast cancer cells
    The synthesis of chalcones as anticancer prodrugs and their bioactivation in CYP1 expressing breast cancer cells Ruparelia, K. C.; Ljaza, T.; Ankrett, D. N.; Wilsher, Nicola Elizabeth; Lodhia, S.; Beresford, Kenneth J. M.; Bhambra, Avninder S.; Arroo, R. R. J.; Potter, G. A.; Butler, P. C.; Tan, Hoon Leong; Zeka, K. Abstract: Background: Although the expression levels of many P450s differ between tumour and corresponding normal tissue, CYP1B1 is one of the few CYP subfamilies which is significantly and consistently overexpressed in tumours. CYP1B1 has been shown to be active within tumours and is capable of metabolising a structurally diverse range of anticancer drugs. Because of this, and its role in the activation of procarcinogens, CYP1B1 is seen as an important target for anticancer drug development. Objectives: To synthesise a series of chalcone derivatives based on the chemopreventative agent DMU-135 and investigate their antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1. Method: A series of chalcones were synthesised in yields of 43-94% using the Claisen-Schmidt condensation reaction. These were screened using a MTT assay against a panel of breast cancer cell lines which have been characterised for CYP1 expression. Results: A number of derivatives showed promising antiproliferative activities in human breast cancer cell lines which express CYP1B1 and CYP1A1, while showing significantly lower toxicity towards a non-tumour breast cell line with no CYP expression. Experiments using the CYP1 inhibitors acacetin and 􀀁-naphthoflavone provided supporting evidence for the involvement of CYP1 enzymes in the bioactivation of these compounds. Conclusions: Chalcones show promise as anticancer agents with evidence suggesting that CYP1 activation of these compounds may be involved. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link

Click here for a full listing of Randolph Arroo's publications and outputs. 

Research interests/expertise

  • Phytochemistry
  • Natural products
  • Pharmacognosy 
  • Alkaloids
  • Lignans
  • Sesquiterpenes
  • Anticancer drugs
  • Malaria 

Areas of teaching

  • Chemistry of medicinal natural products
  • Phytotherapy, complementary and alternative medicine 

Membership of professional associations and societies

Conference attendance

International Symposium on Phytochemicals in Medicine and Food (ISPMF 2015), Shanghai, China, June 26-29 2015 – Invited key note lecture: ‘Dietary Flavonoids and The Prevention of Degenerative Diseases’.

 

University of L'Aquila, Department of Life, Health & Environmental Sciences, L’Aquila, Italy, 13-15 April 2015 – Visiting professor lecture: ‘Chemopreventive effects of orange peel extract’.

 

International Conference on Natural products in Cancer Therapy. Naples, 25-28 June 2013 – Invited key note lecture: ‘Phytoestrogens as natural prodrugs in cancer prevention: Towards a mechanistic model’.

 

Dana Centre/Science Museum, London, 8 November 2012 – Public lecture: ‘Shakespeare's Medicine Cabinet’.

 

International Conference on Natural Anticancer Drugs. Olomouc, Czech Republic, 30 June – 4 July, 2012 – Invited key note lecture: ‘Plant cell factories: Industrial revolution or green revolution?’

 

International Conference of Folk and Herbal Medicine. Udaipur (Rajasthan), 25-27 November, 2010 – Invited key note lecture: ‘Self treatment of malaria with preparations of Artemisia annua Linn.’

Current research students

Saeed Nazir (1st supervisor)

Externally funded research grants information

February 2011 - July 2011 Removal of Chewing Gum using Nut-based Compounds, funded by the EMDA Innovation Fellowship

October 2009 - July 2010 Phytochemicals Conference 2010, funded by paying delegates

July 2009 - August 2009 Antibacterial Compounds from Osha root (Ligusticum porteri), funded by the Nuffield Foundation

August 2008 - September 2008 Exploration of Cow Parsley (Anthriscus Sylvestris) funded by the Nuffield Foundation

March 2006 - April 2010 Development of Artemisia annua Linn as a UK crop for the production of antimalarial medicine, funded by DEFRA-LINK

Professional esteem indicators

  • Phytotherapy Research - Editorial Board
  • Phytochemical Analysis - Editorial Board
  • Plant Resources of Tropical Africa / Medicinal Plants - Co-editor

Case studies

High-artemisia-yielding Artemisia annua cultivars developed in Dr. Arroo's DEFRA-LINK project (see Externally funded research grants information) are now commercially grown in Madagascar.

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