Issued as Interim report, Project no. G-33-63

Zalkow, Leon Harry

English

Scholarly Materials And Research @ Georgia Tech

0̀4iNgiv 	 , :t1. 4X.,:ettf'..- • #1*11:40,4etr00-. Project Title: L 7L.CLML GEORGIA INSTITUTE OF TECHNOLOGY OFFICE OF CONTRACT ADMINISTRATION SPONSORED PROJECT INITIATION Date: 	4/19/78  •L Assigned to: Chemist 1 	 • ' • .7.", Y 	 11 • Defense Priority Rating: None 7r- COPIES TO: ill:7. 0 7 Natural Anti-Tumor Agents form the Senecioneae - Project No: 	G-33•635 Project Director: Dr. Leon H. Zalkow . Sponsor: 	MEW/PHS/NIH - National Cancer Institute; Bethesda, MD 20014 Agreement Period: 	From 	4/1/78 	Until 	3/31/79 (01 year) Type Agreement: Grant No. 1 RO1 CA2327.7-01 	.. 	. 	. Amount: $40,081 New PHS Funds (G-33-635) 7,502 GIT Contribution (G-33-323)' $47,583 Total 	. Reports Required: Annual Progress Reports with Continuation Applications Terminal Progress Report upon Grant Expiration Sponsor Contact Person (s): Technical Matters Moreshwar V. Nadkarni, Ph.D. Division of Cancer Research Resources and Centers 	";; i=ce "004tettliffl. : . National Cancer Institute Bethesda, MD 20014 Contractual Matters (thru OCA) Ms. Marian Focke Grants Management Specialist National Cancer Institute Bethesda, MD 20014 Phone: (301) 496-7444 it Project Director Division Chief (EES) School/Laboratory Director Dean/Director—EES Accounting Office Procurement Office Security Coordinator (OCA) vPieports Coordinator (OCAI Library, Technical Reports Section  EES Information Office 71;,,,siote*811"44',Ri EES Reports & Procedures =  Project File (OCA) :463740taltk ,0114 --- Project Code (GTRI) m  Other 	   CA-3 (3/76) -{E p!7.,7 Likki GPM*. GEORGIA INSTITUTE OF TECHNOLOGY OFFICE OF CONTRACT ADMINISTRATION SPONSORED PROJECT TERMINATION Date: May 23, 1979 Project Title: 	Natural Anti—Tumor Agents From the Senecioneae Project No: 	G-33-635 Project Director: Dr. Leon H. Zalkow Sponsor: 	DHEW/PHS/NIH National Cancer Institute Effective Termination Date: 	3/31/79 (end of 01 Year)  Clearance of Accounting Charges:  3/31/79 for 01 Year  Grant/Contract Closeout Actions Remaining: Final Invoice and Closing Documents Final Fiscal Report Final Report of Inventions Govt. Property Inventory & Related Certificate Classified Material Certificate X Other Annual Report of Expenditures due by 6/30/79 NOTE: FOLLOW—ON PROJECT (02 YEAR) is G- 33-P02. Assigned to: 	 Chemistry  COPIES TO: Project Director Division Chief (EES) School/Laboratory Director Dean/Director—EES Accounting Office Procurement Office Security Coordinator COCA) greports Coordinator (OCAI  (School/Laboratory) Library, Technical Reports Section Office of Computing Services Director, Physical Plant EES Information Office Project File COCA) Project Code (GTRI) Other CA-4 (3/76) TOTAL PROJECT PERIOD FROM 04/01/78 REQUESTED BUDGET PERIOD THROUGH: 03/31/81 _.5 FORM APPROVED 	 JO," 0M9 No. 68-R021)  GRANT NUMBER (INSERT ON ALL PAGES) CA23277-12 6 4008.291 DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE PUBLIC HEALTH SERVICE APPLICATION FOR CONTINUATION GRANT SECTION I REVIEW GROUP SSS TYPE 5 PROGRAM R ) 1 Fizr• to , 04/01/79 	THROUGH: g 3/31/80 TO BE VERIFIED BY APPLICANT. CHECK INFORMATION IN ITEMS 1 THROUGH 0. IF INCORRECT, FURNISH CORRECT INFORMATION IN ITEM 13. 1. TITLE NATURAL ANTITUMOR AGENTS FRO 2k PRINCIPAL INVESTIGATOR OR PROGRAM DIRECTOR (Name and Address, Street, City, State, Zip Code) ZALKOW, LEON H GEORGIA INST OF TECHNOLOGY 225 NORTH AVENUE, N W ATLANTA, GA 30332  28. DEGREE 	 2C. SOCIAL SECURITY NO. 255-36-9515 THE SENECIONEAE 4. APPLICANT ORGANIZATION (Name and Address, Street, City. State. Zip Code) GEORGIA INSTITUTE OF TECHNOLOGY 225 NORTH AVENUE, N W ATLANTA, GA 30332 5. PHS ACCOUNT NUMBER 1586))2123A1 PHD :2D. DEPARTMENT, SERVICE, LABORATORY OR EQUIVALENT SCHOOL OF CHEMISTRY  :2E. MAJOR SUBDIVISION COLL OF SCIS & LIBERAL STUDIES 3. ORGANIZATIONAL COMPONENT TO RECEIVE CREDIT FOR INSTITUTIONAL GRANT PURPOSES 20 OTHER  6. TITLE AND ADDRESS OF OFFICIAL IN BUSINESS OFFICE OF APPLICANT ORGANIZATION DIRECTOR OF FINANCIAL AFFAIRS GEORGIA INSTITUTE OF TECHNOLOGY 225 NORTH AVENUE, N W ATLANTA, GA 30332 COMPLETE THE FOLLOWING (See Instructions) 7. RESEARCH INVOLVING HUMAN SUBJECTS (See Instructions) 	 8. INVENTION CERTIFICATION (See Instructions) MI NO 	IL=I YES 	 MI NO 	 I= YES-NOT PREVIOUSLY APPROVED-  		 REPORTED DATE 1---1 YES-PREVIOUSLY REPORTED 9. PERFORMANCE SITE (S) Georgia Institute of Technolqgy 225 North Avenue, N. W. Atlanta, Goergia 303:32 TELEPHONE INFORMATION 11A. PRINCIPAL INVESTIGATOR OR PROGRAM DIRECTOR (ITEM 2A) AREA CODE 404 TELE. NO. & EXT. 894-4045 404 894-4622 118. NAME OF BUSINESS OFFICIAL (ITEM 6) Frank H. Huff 11C. NAME AND TITLE OF ADMINI-STRATIVE OFFIC'AL (ITEM 158) J. G. Bishop, Jr. Grants & Contracts Off. 	404 894-4814 12B. COUNTY OF APPLICANT ORGANIZATION SHOWN IN ITEM 4 Fulton THROUGH 6. INDICATE THE NUMBER(S) WHERE ANSWER(S) APPLY 10. DIRECT COSTS REQUESTED FOR BUDGET PERIOD $26,161 124. CONGRESSIONAL DISTRICT OF APPLICANT ORGANIZATION SHOWN IN ITEM 4 5th Congressional District 13. USE THIS SPACE FOR CORRECTIONS TO ITEMS 1 2E College of Sciences and Liberal Studies • • 13A RECOMBINANT DNA RESEARCH £X]NO L  ]YES (IF YES c UPDATED MUA REQUIRED) 14. CERTIFICATION AND ACCEPTANCE. 'WE. THE UNDERSIGNED, CERTIFY THAT THE STATEMENTS HEREIN ARE TRUE AND COMPLETE TO THE BEST OF OUR KNOWLEDGE AND ACCEPT, AS TO ANY GRANT AWARDED, THE OBLIGATION TO COMPLY WITH PUBLIC HEALTH SERVICE TERMS AND CONDITIONS IN EFFECT AT THE TIME OF THE AWARD.  1114-1NCIPAUNVESTIGATOR OR PROGRAM DIRECTOR - - ------     DATE SIGNATURES /Signatures required on original copy only. Use ink. 	"Per" 	signatures not' acceptable.)     158. OFFICIAL 546NII,G „KIR AP-P,HeArill ORGAN/ZATIO/     DATE                 PH 5 25913-1 OPTIONAL REV. 4-75 RETURN C MPLETED APPLICATPON PHS AS SOON AS POSSIBLE: SECTION II       SECTION II-BUDGET (USUALLY 12 MONTHS) FROM 4/1/79 THROUGH 3/31/80 GRANT NUMBER CA 23277-02       A. ITEMIZE DIRECT COSTS REQUESTED FOR NEXT BUDGET PERIOD PERSONNEL -  -- - --- TIME OR EFFORT. %/HRS. (c) SALARY REQUESTED (d) FRINGE 	BENEFITS - 	:See 	Instructions) (e) TOTAL (f) —._ NAME 	(Last, 	First. 	Initial) (a) TITLE OF POSITION (b) ...... 	... 	-.,.. „.... , — -,-.. ,...-„,....„ -.7,----,.,---4,,,,,, ,,,,1 ..,...,. .-1,---------.: ,,,,----,--,--, --------- .1-..........,, ,,,,, .„----------.--_. a:_ft---aftg .,----k.,,-==,,,d-- -----=, ....--,,.„--------, ..4. 4....,,,..-- ..e. --...,.-._--)---- ------- .., ..,. .--...---..--..,...„: -.1.-..---".. .., ,-=-- ----. ,„-_..---..--= ..-----------.....--- - ------------_ ,--.._. :„---,- --_,---_   ----,....- .,„---,-.---,,----,__--,,,---,, .,-----......---_--,----- --------- - ---'..-------------- ..---.....--,------, ,-----.----.....------, - - - - - - - -. .  .----,_. - - - - - - - - ----  -   _-- "'"w '' '' - - - - - - - - - - - - - - - w ..----,-----------___^vim ►-ALKOW, LEON H. PRINCIPAL INVESTIGATOR 12.5% , . ,fEttAOR, LESLIE Research Scientist 100%  — _ --- . . — Subtotals -----> S i $ 	21 131 a TOTAL Cortical, cost of each Item listed below) 	 (Columns (d) and (e) 	 ------//' CONSATANT COSTS (See Instructions) S .-..,_.,---..„•-••■-•,----- ...--..._.= "-^-----......- - ..---,------- --.:------" -,,  4-...-- --=-■-•'.- S EQUIPMENT ...-._,.._:..._...._,..„„_,,...„,. - . - - ''' " -, • - 	' -..s- - -^-  " - " -- --- - - -  , - . . . --, - - , '''' - - ' 	." "-• • -'. .- W . - . ' .  ' ---‘ - - "  ---,--w --, ,..---------- -- -%' -.._„,-- ---:-----,-----------", ,,,...------,-,----,-- -- -z..„-,---,.,-,,,---- -,-..--a SUPPLIES Chemicals, Consumable SuppliesSolvents , 	 , Chromatograph Accessories, etc. s 	• 	2 , 080  s 750 TRAVEL DOMESTIC T o• attend scientific meeting FOREIGN . 	i • PATIENT COSTS (See instructions)  r.,..• 	Ae,b $ ALTERATIONS AND RENOVATIONS  $ OTHER EXPENSES (Itemize) Plant collecting, grinding, handling & shipping - • "e.,-. .-st-i-....-1-- -'..7.. i.,-(4=,;..'-=S-1 -.. .:.--,---:--.---- ...-..._—_-- ...„-,...-W-. ---2..!----- -- ..c.=,.....,... ,....r..- 8 2,200 s 26,161 TOTAL DIRECT COST (Enter on Page 1, Item 10) INDIRECT COST (Set' Instructions) _ 	70_1/4 nye 	 Date of DHEW Agreement: 	 ❑ Not Requested _____% TDC• 	 July 11, 	1978 	 ❑ Under negotiation with: • If this is a special rate (e.g. off•slte), explain 	  PAGE 2 PHS-25)0-1 (Formerly NIH-2C06-1 ) (Rev. 4-75) SECTION III SECTION ill-FISCAL DATA FOR CURRENT BUDGET PERIOD (USUALLY 12 MONTHS) FROM April 1, 1978 THROUGH March 31,1979 GRANT NUMBER CA 23277-02 The following pertains to your CURRENT PHS budget. Do not include cost sharing funds. This information in conjunction with that provided on Page 2 will be used in determining the amount of support for the NEXT budget period. A. BUDGET CATEGORIES CURRENT BUDGET (As approved by awarding unit) (1) ACTUAL EXPENDITURES  IHRU 2 /3/ bR ESTIMATED ADDITIONAL EXPENDITURES AND OBLIGATIONS FOR REMAINDER OF CURRENT BUDGET PERIOD (3) TOTAL ESTIMATED EXPENDITURES AND OBLIGATIONS (Col. 2 plus Col. 3) (4) ESTIMATED UNOBLIGATED BALANCE (Subtract Col. 4 from Col. 1) (5) (Insert Date) (2) Personnel (Salaries) 18,230 13,692 4,538 18,230 0 Fringe Benefits 1,705 1,073 632 1,705 0 Consultant Costs - - _ ... _ - .... - -. Equipment 3,000 3,000 0 3,000 0 supplies 2,000 587 1,413 2,000 0 TRAVEL Domestic 750 750 0 750 0 Foreign -- -- -- -- -- Patient Costs -- -- -- -- - Alterations and Renovations -- - - __ .. Other 2,000 619 1,381 2,000 0 Total Direct Costs 27,585 19 721 7,964 27,685 0 Indirect Costs (If included in award) 12,396 10,406 1,990 12,396 0 . TOTALS $40,081 $30,127 $ 	9,954 $40,081 $ 	0 Use space below to: B. List all items of equipment purchased or expected to be purchased during this budget period which have a unit cost of $1000 or more. C. Explain any significant balance or deficit shown in any category of Column 5. D. List all other research support for Principal Investigator by source, project title, and annual ' , mount. B. A total of $3,619 ($3,000 from original equipment budget and $619 transferred to equipment category from other expenses) was used as part of a total purchase of $11,000 for a Waters 500 Preparative Liquid Chromatograph. We expect to spend an additional $2,000 from this grant for partial payment (total cost $3,100) of a Waters Model R401 differential diffractometer for a liquid 	. chromatograph. 4 PAGE3 	(,Use Continuation Pages as necessary) PHS4590-1(Formerly NIH-2006-1) (Rev. 4- APPLICANT: REPEAT GRANT NUMBER SHOWN ON PAGE 1 --aw SECTION IV—SUMMARY PROGRESS REPORT GRANT NUMBER CA23277-02 PRINCIPAL INVESTIGATOR OR PROGRAM DIRECTOR (Last Fkst Zalkow, Leon H. NAME OF ORGANIZATION Georgia Institute of Technology PERIOD COVERED BY THIS REPORT FROM 4/1/78 THROUGH 1/1/79 SECTION IV TITLE (Repeat title shown In Item I on first page) Natural Antitumor Agents from the Senecioneae I. List publications: (a) published and not previously reported; (b) in press. Provide five reprints if not previously submitted. 2. List all additions and deletions in professional personnel and any changes in effort. 3. Progress Report. (See Instructions) 1. L. Gelbaum and L. H. Zalkow, "Secondary Plant Metabolites from Senecio smallii." 30th Southeastern Regional Meeting, American Chemical Society, Savannah, Georgia Nov. 8-10, 1978. 2. During the period covered, the following personnel devoted the indicated amounts of time. There will be no change except that Dr. H. Deutsch will not continue on this project. Dr. L. Gelbaum,Research Scientist, 100% time. Dr. H. Deutsch, Research Scientist, 25% time. Ms. S. Bonetti, B.S., technician, 50% time. 3. During the period April 1, 1978 - Jan. 1, 1979, we have worked on the extracts from Senecio small-Li and Crotalaria spectablis. The extracts of these plants have been submitted for screening by the National Cancer Institute (NCI). Preliminary reports indicate that the 95% ethanol extract from S. smallii showed the activity indicated below: Test System Toxd. Surv. Sex M M M M F F F F Dose T/C PS II II rI 06/06 • 	 II rr 06/06 400 200 100 50 600 400 265 175 132 122 120 107 129 128 133 132 KB 	2.7 X 10(1) The aqueous methanol partition from the plant further concentrated the active component as shown by the KB screen value of 2.8 X 10(0). Further separation and screening are in progress. By high performance liquid chromatography (HPLC) we have thus far isolated and determined the structures of the following compounds from S. smallii: ethyl-l-hydroxy•4-oxo-2,5-cyclohexadiene-l-acetate (1),14-oxo-1,2-dehydro-cacalol methyl ether (2), and the pyrrolizidine alkaloids senecionine (3), senkirkine (4),and retrosine (5). Very efficient means have been developed for the separation of polar compounds such as pyrrolizidine alkaloids on reverse phase columns using HPLC and we have developed oneof the most efficient laboratories in the country for separation of natural products by HPLC. A large quantity of Crotolaria spectabilis seeds were collected in south Georgia and over 100 g of the pyrrolizidine alkaloid monocrotaline (6) was isolated from these seeds. Hydrolysis of this alkaloid, led in good yield to the -necine base retronecine (7) which is being used in the synthesis of semi-_ PAGEilw (Use Continuation Pills as mussy) PHS-2590-1 (Formerly N I H-2006-1 ) (Rev. 4- 75) 1 	2 H3C H OH H ,CH 3-C-C-CH 3 H,C CO 	/ CO  0 CHr-o H 	H 3C H OH / • \C ''''Cli2...C-C-CH 3 / 	HsC CO 	CO 0 0 	3 -‘--(:) H H3C H OH \ 	N / e c--"c}12-c-c-cH2 OH / I ‘ H3C CO 	CO / 0 cH2---0  CH3 3 4 5 H 3C OH CH 3-CH —C—C-C H 3 I 	I CO OH CO 0 CH 2-0 HO CH2OH C7 C601<:8 • r\i ILY°  C5 	 N1 Figure II Zalkow, Leon H. 255-36-9515 3. (Continued) synthetic pyrrolizidine alkaloids. In this synthetic work it is anticipated that increased activity over the purely natural active pyrrolizidine alkaloids such as indicine N-oxide will be realized by a study of structure--activity relationships. During this period we have begun a compilation of "C NMR data on pyrrolizi-dine alkaloids which allows rapid structural and stereochemical assignments. Like-wise, we have utilized single crystal x-ray analysis routinely when suitable crystals were available and structures 2 and 7 were arrived at by this method. Figures I and II show the computer drawn structures of 2 and 7 respectively as arrived at from the x-ray data. During the next grant period we expect to continue work on the above mentioned plants and, in addition, we expect to initiate work on the following plants of the Senecio genus as recommended by Dr. T. M. Barkley of Kansas State University: Section AUREI Senecio pseudaureaus Senecio dimorphophyllus Senecio streptanthifoZius Section LOBATI Sececio multilobatus Section TOMENTOSI Senecio werneriaefolius Senecio canus Section LUGENTES Senecio atratus Senecio wootonii Section INTEGERRIMI Senecio intergerriumus Section APLECTENTES Senecio amplectens Senecio bigelovii Section SUFFRUTICOSI Senecio dougZasii Senecio spartioides Section TRIANGULARES Senecio fremontii Senecio triangularis Senecio eremophilus The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application. I/ Zy ;7 Date   Principal Inl:ettigator  Texts: Horowtiz and Sahni, Fundamentals of Data Structur e s  Knuth, The Art of Computer Programming, Vol. 1 Remedial Course: ICS 3113 Computer Systems  Knowledge of hardware and software components of digital computer systems including system architecture and or-ganization, input/output, data representation, storage interrupts, parallel processing, microprogramming, minicom-puters, and basic systems software such as language proces-sors and multiprogramming operating systems. Texts: Bell and Newell• Computer Structures: Readings  and Examples  Freeman, Software Systems Principles  Remedial Course: ICS 3705 

Natural anti-tumor agents from the Senecioneae

Issued as Summary progress report, Project no. G-33-P0

Natural antitumor agents from the Senecioneae

https://smartech.gatech.edu/bitstream/1853/40084/1/g-33-635_146196.pdf

Natural anti-tumor agents from the Senecioneae

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Scholarly Materials And Research @ Georgia Tech

Scholarly Materials And Research @ Georgia Tech