This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT This research project forges collaborations between a junior investigator (Cooperwood) and senior investigators (Du, Redda and Ablordeppey) who have vast knowledge in research. While some success in the treatment of breast cancer have been attained in the recent years through early detection and adjuvant systemic treatment, the incidence of this disease has steadily been on the incline. Endocrine therapy has been proven to be effective against estrogen receptor (ER) positive breast cancer through antagonism of estrogen at its receptor. We plan to target the ER using steroidal base compounds and flavonoids. We have several compounds, which have been designed and synthesized with inhibitory activity against MCF-7 breast cancer cells similar to that 4-hydroxytamoxifen. Another drug targeted disease state of interest is MRSA infections. Drs. Cooperwood, Du and Ablordeppey are involved in research concerning design of potential drugs for the treatment of MRSA and other infections. Among the major pathogens responsible for nosocomial infections is Staphylococcus aureus. Antibiotics have become less effective against S. aureus because the bacteria mutate to resist current treatments. While attempts to obtain vaccines are in the works, there is a need to develop new drugs against S. aureus, and more specifically against MRSA. Hypotheses: The design and synthesis of anti-breast cancer agents are based upon our FlexX molecular model. All of test compounds with MCF-7 inhibitory growth activity have rigid structures (steroids mentioned in preliminary studies) bearing two hydroxyl groups with a separation distance similar to that of estradiol with one hydroxyl group forming an alkylamino ether. We conceptualize that it may be possible to improve MCF-7 inhibitory growth activity by extension of alkylamino side chain. Furthermore, our FlexX molecular model strongly suggests that these concepts can be applied to other rigid structures such as flavonoids and chalcones. The design and synthesis of anti-Methicillin Resistant Staphylococcus aureus (MRSA) bacteria agents are based upon previously synthesized compounds that displayed activity. We conceptualize that by changing the electronic and hydrophobic characteristic of substituents on the phenyl portion of N-alkyl 3- Phenylthioquinolinium will improve potency and reduce cytotoxicity. The goals of this pilot are to design synthesis and develop drug candidates with activities against breast cancer and anti-MRSA agents. To achieve these goals, we will elicit the collaboration of individuals who have an invested interest in various disease states to carry out the specific aims which are to (1) design, synthesize and evaluate the pharmacological activities of compounds as potential anti-breast cancer, anti-Methicillin-Resistant Staphylococcus aureus (MRSA);and (2) lead compound(s) optimization based upon pharmacological activities and molecular modeling studies.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Research Centers in Minority Institutions Award (G12)
Project #
Application #
Study Section
Special Emphasis Panel (ZRR1-RI-3 (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Florida Agricultural and Mechanical University
Schools of Pharmacy
United States
Zip Code
Poku, Rosemary A; Salako, Olufisayo O; Amissah, Felix et al. (2017) Polyisoprenylated cysteinyl amide inhibitors induce caspase 3/7- and 8-mediated apoptosis and inhibit migration and invasion of metastatic prostate cancer cells. Am J Cancer Res 7:1515-1527
Ntantie, Elizabeth; Fletcher, Jerrine; Amissah, Felix et al. (2017) Polyisoprenylated cysteinyl amide inhibitors disrupt actin cytoskeleton organization, induce cell rounding and block migration of non-small cell lung cancer. Oncotarget 8:31726-31744
Mazzio, Elizabeth A; Soliman, Karam F A (2017) HTP Nutraceutical Screening for Histone Deacetylase Inhibitors and Effects of HDACis on Tumor-suppressing miRNAs by Trichostatin A and Grapeseed (Vitis vinifera) in HeLa cells. Cancer Genomics Proteomics 14:17-33
Archibong, Edikan; Foster, Alexander; Caldwell, Keirsten et al. (2016) Synthesis, characterization, and electrospinning of novel polyaniline-peptide polymers. Appl Mater Today 4:78-82
Ofori, Edward; Zhu, Xue Y; Etukala, Jagan R et al. (2016) Design and synthesis of dual 5-HT1A and 5-HT7 receptor ligands. Bioorg Med Chem 24:3464-71
Mathis, Arlesia; Rooks, Ronica; Kruger, Daniel (2016) Improving the Neighborhood Environment for Urban Older Adults: Social Context and Self-Rated Health. Int J Environ Res Public Health 13:ijerph13010003
Godugu, Chandraiah; Doddapaneni, Ravi; Patel, Apurva R et al. (2016) Novel Gefitinib Formulation with Improved Oral Bioavailability in Treatment of A431 Skin Carcinoma. Pharm Res 33:137-54
Mochona, Bereket; Jackson, Timothy; McCauley, DeCoria et al. (2016) Synthesis and Cytotoxic Evaluation of Pyrrole Hetarylazoles Containing Benzimidazole/Pyrazolone/1,3,4-Oxadiazole Motifs. J Heterocycl Chem 53:1871-1877
Mazzio, Elizabeth A; Li, Nan; Bauer, David et al. (2016) Natural product HTP screening for antibacterial (E.coli 0157:H7) and anti-inflammatory agents in (LPS from E. coli O111:B4) activated macrophages and microglial cells; focus on sepsis. BMC Complement Altern Med 16:467
Etukala, Jagan R; Zhu, Xue Y; Eyunni, Suresh V K et al. (2016) Development of CNS multi-receptor ligands: Modification of known D2 pharmacophores. Bioorg Med Chem 24:3671-9

Showing the most recent 10 out of 204 publications