Drug Discovery in Africa: Impacts of Genomics, Natural Products, Traditional Medicines, Insights into Medicinal Chemistry, and Technology Platforms in Pursuit of New Drugs

453 Pages·2012·7.69 MB·English

by  Barthélemy Nyasse (auth.)

Drug Discovery in Africa
.
Kelly Chibale (cid:129) Mike Davies-Coleman (cid:129)
Collen Masimirembwa
Editors
Drug Discovery in Africa
Impacts of Genomics, Natural Products,
Traditional Medicines, Insights into
Medicinal Chemistry, and Technology
Platforms in Pursuit of New Drugs
Editors
KellyChibale MikeDavies-Coleman
Dept.ofChemistry DepartmentofChemistry
UniversityofCapeTown RhodesUniversity
Rondebosch Grahamstown
SouthAfrica SouthAfrica
CollenMasimirembwa
AfricanInstituteofBiomedicalScience
andTechnology
Harare
Zimbabwe
ISBN978-3-642-28174-7 ISBN978-3-642-28175-4(eBook)
DOI10.1007/978-3-642-28175-4
SpringerHeidelbergNewYorkDordrechtLondon
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ProfessorJohnsonJato.ATribute
OnJune27,2012,weweredeeplysaddenedtohearofthepassinginhissleepof
ourdearfriendandcolleague,JohnsonJato,athishomeinYaounde,Cameroon.
InChap.2,wediscusssomeofthesignificantandnoveldrugleadsdiscovered
from African biodiversity in the US National Cancer Institute (NCI) program. In
launchingtheNCIplantcollectionprograminCameroonin1986throughacontract
with MissouriBotanicalGarden (MBG), Professor JohnsonJatooftheUniversity
ofYaoundeprovedtobethekeycontactforboththeNCIandMBG,andprominent
amongthedrugleadsdiscoveredwerethepotentialanti-HIVagent,michellamine
B,andtheantitumoragents,theschweinfurthins.
Dr.JamesMiller,whoatthattimewasoneofthemainMBGinvestigators,now
Dean and Vice President for Research at New York Botanical Garden, remarked
—“Johnson was tremendously helpful in a country that is often confusing and
difficult, and he helped us navigate everything from basic logistics to difficult
politics. My most vivid memory of Johnson was that he always did it all in a
tremendouslycheerful, optimisticwaywithagreatsenseofhumor.Wecouldnot
haveaccomplishedwhatwedidwithouthishelp.”RegardingthemichellamineB
project and the cultivation of Ancistrocladus korupensis, Dr. James Simon, who
supervisedtheprojectwhileatPurdueUniversity,noted—“Johnsondidseemtobe
ageless with a super-sized heart of gold and always optimistic (or nearly always
anyway). I remember him quite vividly and his leadership in the michellamine B
project was instrumental in the ability for all of us to do the work, do it well and
navigate it all through the complexities found out there (in Cameroon). He was a
generous soul.” In the schweinfurthin project, it was the successful scale-up
recollectionsundertakenbyProfessorJatoinCameroonin1998–1999thatpermit-
tedtheongoingpreclinicalstudiesofschweinfurthinanaloguestoproceed.
ThefirstinteractionbetweenJohnsonandtheNCIwaswhenhevisitedDr.Joe
Mayo, Chief of the Biological Testing Branch, in the early 1980s to discuss the
possibilityofNCIhelpingwithestablishingsomepreclinicaltestingattheUniver-
sityofYaounde1.Whilenoformalcollaborationwasestablished,JohnsonandJoe
becameclosepersonalfriends,andJoedevelopedahugeadmirationforthelevelof
researchJohnsonachievedwithverylimitedresources.Theirfriendshipcontinued
overtheyears,andin1986,whentheNCIestablishedtheplantcollectioncontract
withMBG,JoeintroducedJohnsontoGordonasapossiblecontactinCameroon.
JohnsonandGordonbecamefirmfriendsandcolleaguesandcollaboratedcloselyin
thevariousNCIprojectsinCameroon.Thiscloserelationshipextendedtoallofus,
andwekeptincontactwithJohnsonrighttotheend.WeallrememberJohnsonas
an ever-cheerful friend and a resourceful and reliable colleague who approached
every project with a determined optimism which enabled him to overcome seem-
inglyinsurmountablechallenges,andwhichearnedhimtherespectandadmiration
ofallhiscolleagues.Wecantrulysaywecouldnothaveaccomplishedwhatwedid
withouthishelpandinspiration.Thankyou,Johnson.Wewillmissyou!
JohnBeutler,GordonCragg,andDavidNewman
Foreword
African Drug Discovery: A Window on the World
Africa is a continent of tremendous opportunity: a wealth of natural resources,
people talent and energy. However, there is also a great burden of neglected
diseases,notonlyintermsofsufferingandliveslost,butalsoasalossofeconomic
value. Some of these diseases are shared with the Western world, but many are
eitherespeciallyprevalenttoAfrica,orevenuniquetothecontinent.
Thisbookrepresentsarayofhopeatadifficulttime.Itisawindowontheworld
of African science, and the perspective on the discovery and progression of new
medicinestotargetkeydiseases.Bringingtogethersomeofthebestresearchersin
Africa with a common goal, to focus on how to develop new medicines in an
African context. Drug discovery and development requires being able to pull
together people with a wide variety of expertise and background, to form teams
with a common goal. It means bringing together the basic science and medical
research.Itmeansbridgingthegapbetweenscienceandtechnology.
But those who invest in new medicines must also have deep pockets, and great
patience. Even with the best will in the world, a new pharmaceutical can take a
decadetobebroughtthroughthedevelopmentpathway.Traditionally,thisresearch
haslargelybeenfundedfromoutsideAfrica;whatarethesignsthatthepoliticalwill
hereischanging?In2006intheKhartoumdeclaration[1],membersoftheAfrican
Unionsetatargettoinvest1%oftheirgrossdomesticproductinR&D.Thistargetis
metbythreeverydifferentcountries—Malawi,UgandaandSouthAfrica—sothere
iseveryreasontohopethatmorewillfollowifthereisthepoliticalwill[2].There
wasalsoacallfortheestablishmentofcentresofexcellenceinAfrica.Howmanyof
thosewillfeedintotheoverallobjectiveofnewmedicinesisnotclearyet.However,
the establishment of ANDi (the African Network for New Drug and Diagnostic
Innovation)[3]issurelyanimportantmilestoneinthisprocess.TheCairodeclaration
oftheAfricanMinisterialCouncilonScienceandTechnology(AMCOST)[4]made
two other strong recommendations: support of South-Southcooperation inscience,
technology and innovation and the establishment of a Pan-African Intellectual
vii
viii Foreword
Property Organization (PAIPO). This book contains many examples of the former
andhopefullysowstheseedsforthelatter.
Atatimewhentheproductivityofthepharmaceuticalindustryisstatic,andits
financialstariswaning,itispertinenttoaskwhyofalltechnologiesthecountriesin
Africa should prioritise investments in new medicines. One key to success in the
identificationofnewmedicinesistheproximitytopatients,havingresearcherswho
understandonadailybasisthedevastatingeffectsofthediseasestheyaretackling.
Africanapproachestoneglecteddiseasewillnotonlycomefromtheheart,butwill
have this insight. Second, the patrimony of the continent is its natural resources,
whichcanbeusedforthebenefitofallAfrica’speople.Weneedtoworkalongside
traditional healers to understand these products better [5]. We need to follow the
Chinese approach of dao-xing-ni-shi (acting in the reversed direction): [6] use
observational clinical studies to improve our clinical understanding of how these
natural products work, before becoming too reductionist. These natural products
haveexistedsidebysidewiththepopulationforgenerations,andsotheinformation
knownabouttheirclinicalaspectsiscritical.Thetraditionalremediesofyesterday
havebeenimprovedbytheskillsofourchemists,pharmacologistsandphysicians
intothemedicinesoftoday[7].Inasimilarway,thetraditionalremediesoftoday
containtheseedsoftheideasforthemedicinesfortomorrow.Thefocusonnatural
productsfromAfricaisclearinthisbook;halfthechaptersarededicatedtosome
aspect of the work. We need to develop an African way forward for natural
products. They key here is that the way these products are moved forward must
beseenfromanAfricanperspective.Wemustavoidthetendencyto‘cutandpaste’
thewesternexperienceofdrugdevelopment.
Ultimately, science is about people, and developing a new generation of
scientists.Beyondfunding,thisrequirestrainingofthenextgenerationofscientists,
andopportunitiesforscientificexchangebetweencountries[8].Itismyhopethat
thereadersofthisbookwillbenefitnotonlyfromthescientificcontent,butfromthe
improved visibility and interaction with the new generation of African science
leaders.Ultimately,thechancetochangethefutureofAfricaisintheirhands.The
windowonAfricanscienceisopen;weneedtoallworktogethertokeepitthatway.
TimWells
ChiefScientificOfficer
MedicinesforMalariaVenture
Geneva
Switzerland
References
1. EX. CL/Dec.254 (VIII) http://www.africa-union.org/root/au/Documents/
Decisions/com/AU6th_ord_Council_Decisions_Jan2006_Khartoum.pdf
2. UNESCOworldScienceReport
Foreword ix
3. http://www.andi-africa.org/
4. http://www.nepadst.org/doclibrary/pdfs/cairo_declaration_2006.pdf
5. WillcoxML,GrazB,FalquetJ,DiakiteC,GianiS,DialloD(2011)A“reverse
pharmacology”approachfordevelopingananti-malarialphytomedicine.Malar
J10(Suppl1):S8
6. Lei SH (1999) From Changshan to a new antimalarial drug. Soc Stud Sci
29:323–358
7. Wells TNC (2011) Natural products as starting points for future anti-malarial
therapies:goingbacktoourroots?MalarJ10(Suppl1):S3
8. MurenziR(2011)Givethenewgenerationachance.Nature474:543