Abstract

Cancer is an emerging public health problem in Africa and the world all over coupled with toxicity and the emergence of resistance to most of the existing drugs. This motivated our search for agents from Citrus reticulta which could serve as leads for the development of effective, less toxic and affordable anticancer agents.

This plant was chosen on the basis of its use in folk medicine in the treatment of cancer. Repeated column chromatography of the methylene chloride extract of the fruit peels afforded ten compounds, three of which have been completely identified as: stigmasterol, tangeretin and nobiletin.

Four (AGN6, AGN7, AGN9 and AGN10) out of the ten compounds were tested for in vitro activity against lung cancer. Three of them were active. Among the active compounds one was identified as nobiletin. The structures of the compounds were determined using spectroscopic techniques (MS and NMR analysis), physical characteristics and comparison of their data with literature values. The CH2Cl2 extract exhibited anticancer activity while the MeOH extract did not.

CHAPTER ONE

LITERATURE REVIEW

1.1 Introduction

Natural products especially those derived from plants have been used for the treatment of diseases for thousands of years. The use of plants in the indigenous cultures particularly in developing countries are numerous and diverse, forming an important socio-economic base including their uses as anticancer agents. The World Health Organization (WHO) estimates that up to 80% of the world’s population in developing countries depends on locally available plant sources for their primary healthcare, since western pharmaceuticals are often expensive or inaccessible (Ezekiel, 2014).

Plant   based drugs have been isolated or derived from natural sources based on their uses in traditional medicine as herbal remedies or crude drug. In the area of cancer treatment, many claims have been made for the beneficial effects of plants though many of the claims have not been verified since cancer as a specific disease is poorly defined in terms of folklore and traditional medicine.

Nevertheless, the discovery and the development of efficacious anticancer agents such as vinblastine (1) and vincristine (2) isolated from the Madagascar periwinkle, Catharanthus roseus,taxol (3) from the bark of the pacific yew, Taxus brevifolia provided convincing evidence that plant could be a source of novel  cancer chemotherapeutic agents (Shoeb et al., 2006).While the natural  product isolated  as the active compound might not be suitable for development as an effective drug, it can provide a suitable lead for conversion into a clinically useful agent.

Many potential medicinal plants are endemic to particular regions of the world. Thus in an attempt to prevent the extinction of these medicinal plants to render the treatment of illnesses and to make available the active principles found in them to patients all over the world, organic chemists have undertaken the task in conjunction with traditional healers and biologist to collect the plants, to isolate and purify its constituents, elucidate their structures and test for active principles.

The potentially in vitro active candidates are subjected to clinical trials and may even be synthesized from readily available simple reagents. This is why the Natural Product Chemistry Research Group at the University of Buea, in collaboration with other groups embarked on the phytochemical study of a Cameroonian plant C. reticulata with particular attention to isolate lead compounds for drugs against Cancer.

1.2   Rationale

In spite of the availability of a large number of anticancer drugs and various chemotherapeutic options, cancer still remains a life threatening disease and with the emergence of cancer resistance to most of the existing drugs (Genevieve et al., 2014), thus there is an urgent need to develop new effective, less toxic and affordable anticancer drugs.

Plants are an important source of novel molecules for the development of new anticancer agents to counter the increasing resistance of cancer diseases. Citrus reticulata is reported to contain phytonutrients which show activities against cancer (Priya et al., 2014, Ezekiel, 2014). Thus there is the need to do a detailed study of this plant in order to isolate the active principles responsible for its anticancer activity. These findings motivated our search for novel potential candidate molecules for the development of   new, safe and efficacious anticancer agents from the peels of Citrus reticulata.

1.3 Hypothesis

Citrus reticulata contains bioactive compounds potent against cancer that may serve as lead compounds for the development of anticancer agents.

1.4 Overall Objective

The overall objective of this research were to search for agents from C. reticulata which could serve as lead compounds for the development of less toxic and affordable anticancer drugs.

1.5 Specific Objectives were to;

1. Identify, collect and process the plant material
2. Prepare and carry out preliminary screening of crude extracts in collaboration with biologists.
3. Carry out bioassay-guided fractionation and to isolate the secondary metabolites from Citrus reticulata peels using chromatographic techniques.
4. Characterized the isolated constituents using various spectroscopic techniques and to test the compounds for anticancer activities.