NETS-ACS 613th Meeting
Developing Pharmaceutical Agents: Metal Complexes With Thiosemicarbazones As Ligands
Date: Thursday, February 28, 2013
Location: Eastman Lodge
Agenda
6:15 PM Social gathering
6:30 PM Dinner
7:15 PM Program
Menu
Broasted Chicken or Baked Ham
Green Beans, Baked Beans, Cole Slaw
Texas Toast
Chocolate or Coconut Cream Pie
Tea or Lemonade
The cost for the meal is $15/person, half price for students. Make check payable to "NETSACS". Indicate the number in your party. RSVP's are fine with the understanding that payment will be made at the meeting. No cost to attend the lecture only.
Please RSVP by 4:00pm on February 25, 2013.Please reply to:
Erica Edmisten
(423) 229-6920 / Next Meeting on March 21, 2013, at the Lodge, Dr. Richard Wolfe will present “Carbonite: A Greener and Cleaner Form of Coal”.
Directions to the Eastman Lodge:
Use I-26 – Take Exit 3 for Meadowview Parkway.
Turn west, going under I-26 on Meadowview Parkway / Reservoir Road.
The name of the road will become only Reservoir Road.
Go 2.3 miles and turn right on Bays Mountain Park Road.
You should see a sign for Bays Mountain Park.
Take the right fork in the road in 0.2 miles to the Lodge.
Thiosemicarbazone
ABSTRACT:
With a number of platinum compounds now in clinical use, coordination complexes are still actively being studied for use as chemotherapeutics. Gallium is considered to be the second metal (after platinum) to have generated much research interest. The attractiveness of gallium as a therapeutic agent stems primarily from its biological and chemical mimicry of iron. Stabilization of Ga(III) relative to hydrolysis can be achieved by coordination to chelating organic ligands. In addition the investigation of ruthenium (Ru) complexes as potential pharmaceutical agents is continuing to attract increasing attention. This is due in part to inherent chemical properties of such compounds. As examples, two Ru(III) complexes, namely NAMI-A ([ImH][(Im)RuCl4(dmso)], Im = imidazole) and KP1019 ([IndH][(Ind)2RuCl4], Ind = indazole) have recently completed Phase I clinical trials as anti-metastatic and anticancer drugs, respectively. Another class of Ru complexes that is generating significant interest is the organometallic complexes [(arene)Ru(LL)Cl]+. Though these complexes have yet to be clinically assessed, they show wide ranging medicinal properties. This is due to their structure which provides an ideal template for modification in order to generate medicinally-active compounds. In particular variation of the arene and/or the LL ancillary ligand provides potentially extensive variations in both geometry and electronic properties. In our research lab we synthesize complexes of this type where LL = a thiosemicarbazone. Thiosemicarbazones are well-known in medicinal chemistry as bioactive compounds showing a broad spectrum of chemotherapeutic properties. The arenes we use are p-cymene and benzene but we have also been investigating the use of 1,4,7-trithiacyclononane (9aneS3) as an alternative face-cap to the arenes. Our compounds are evaluated for their anticancer and antibacterial properties. In addition their biochemical and biophysical characteristics are investigated through their reactions with nucleic acids and model proteins.
Speaker:
Floyd Beckford received a BS (with honors) and a PhD in inorganic chemistry from the University of the West Indies, Mona Campus (Jamaica). Following his post-doctoral work at Texas A&M University at College Station he taught at the University of Toledo as a visiting professor for two years. He then taught at Lyon College in Arkansas where he rose to the rank of professor. He joined the faculty of the University of Virginia’s College at Wise in August, 2012 where he holds the Daniel Chair in Chemistry with the rank of professor.
His graduate work focused on the mechanisms of the reactions of iron-cyano complexes with biological reductants, particularly ascorbic acid and cysteine. The iron complexes contained an unusual di-cyano bridge between two iron(III) centers which afforded the compounds very rich redox behavior. After his graduate work he undertook postdoctoral work at Texas A&M University at College Station working in the field of water-soluble organometallic chemistry. The project focused mainly on the synthesis of organometallic ruthenium clusters of the type Ru3(CO)9(L)3 where L is the water-soluble ligand 1,3,5-triaza-7-phosphaadamantane (PTA). This ligand is now the core of a new and impressive class of organometallic complexes, ([(η6-arene)Ru(PTA)(Cl)2], that show significant anti-metastatic activity.
His current research interest lies in developing a similar class of drugs, [(η6-arene)Ru(LL)Cl]+, that utilizes biologically active compounds as ligands (LL). In particular a class of Schiff bases known as thiosemicarbazones and more recently curcuminoids which are derivatives of curcumin are the focus. These ligands have wide ranging biological properties that are enhanced in metal ion complexes. This drug development process is a multi-disciplinary approach which includes chemistry, biology and medicine. Consequently his research involves synthesis of inorganic compounds, their characterization and their biophysical and biochemical characteristics. The compounds are also assayed for anticancer and antibacterial activity.