Abstract

By employing the natural product quinic acid as starting material, a series of synthetic small molecule macrolides reminiscent of the cell migration inhibitor migrastatin were synthesized and characterized as antibiotics and tumor cell migration inhibitors. Three of the macrolides were shown to inhibit 4T1 breast cancer cell migration with low nanomolar to sub-micromolar IC50 values (ranging from 70-500 nM) in complementary assays including a quantitative cell migration assay and a semiquantitative wound healing assay. In a separate study, a quinic acid scaffold was used to build a small library of mycothiol analogs and shown to be low to sub-micromolar inhibitors of the mycobacterium detoxification enzyme mycothiol-S-conjugate amidase. Structural studies on natural product and natural product-like inhibitors of mycobacterial enzymes are ongoing.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK031135-01
Application #
7593532
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2007
Total Cost
$400,482
Indirect Cost

  Institution

Name
National Institute of Diabetes and Digestive and Kidney Diseases
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Sclafani, Anthony; Vural, Austin S; Ackroff, Karen (2018) Profound differences in fat versus carbohydrate preferences in CAST/EiJ and C57BL/6J mice: Role of fat taste. Physiol Behav 194:348-355
Sclafani, Anthony (2018) From appetite setpoint to appetition: 50years of ingestive behavior research. Physiol Behav 192:210-217
Sclafani, Anthony; Ackroff, Karen (2017) Flavor preferences conditioned by nutritive and non-nutritive sweeteners in mice. Physiol Behav 173:188-199
Davison, Jack R; Lohith, Katheryn M; Wang, Xiaoning et al. (2017) A New Natural Product Analog of Blasticidin S Reveals Cellular Uptake Facilitated by the NorA Multidrug Transporter. Antimicrob Agents Chemother 61:
Sclafani, Anthony; Adamantidis, Antoine; Ackroff, Karen (2016) MCH receptor deletion does not impair glucose-conditioned flavor preferences in mice. Physiol Behav 163:239-244
Kraft, Tamar T; Huang, Donald; Lolier, Melanie et al. (2016) BALB/c and SWR inbred mice differ in post-oral fructose appetition as revealed by sugar versus non-nutritive sweetener tests. Physiol Behav 153:64-9
Ackroff, Karen; Sclafani, Anthony (2016) Maltodextrin and sucrose preferences in sweet-sensitive (C57BL/6J) and subsensitive (129P3/J) mice revisited. Physiol Behav 165:286-90
Sclafani, Anthony; Ackroff, Karen (2016) Operant licking for intragastric sugar infusions: Differential reinforcing actions of glucose, sucrose and fructose in mice. Physiol Behav 153:115-24
Sclafani, Anthony; Touzani, Khalid; Ackroff, Karen (2015) Intragastric fat self-administration is impaired in GPR40/120 double knockout mice. Physiol Behav 147:141-8
Sclafani, Anthony; Ackroff, Karen (2015) Flavor preference conditioning by different sugars in sweet ageusic Trpm5 knockout mice. Physiol Behav 140:156-63

Showing the most recent 10 out of 31 publications