Madhavi Sriram
Baylor University
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Featured researches published by Madhavi Sriram.
Bioorganic & Medicinal Chemistry | 2008
Madhavi Sriram; John J. Hall; Nathan C. Grohmann; Tracy E. Strecker; Taylor Wootton; Andreas Franken; Mary Lynn Trawick; Kevin G. Pinney
A novel series of dihydronaphthalene and benzosuberene analogs bearing structural similarity to the combretastatins in terms of 1,2-diarylethene, trimethoxyphenyl, and biaryl functionality has been synthesized. The compounds have been evaluated in regard to their ability to inhibit tubulin assembly and for their cytotoxicity against selected human cancer cell lines. From this series of compounds, benzosuberene analogs 2 and 4 inhibited tubulin assembly at concentrations comparable to that of combretastatin A-4 (CA4) and combretastatin A-1 (CA1). Furthermore, analog 4 demonstrated remarkable cytotoxicity against the three human cancer cell lines evaluated (for example GI(50)=0.0000032 microM against DU-145 prostate carcinoma).
Journal of Natural Products | 2013
Mallinath B. Hadimani; Matthew T. MacDonough; Anjan Ghatak; Tracy E. Strecker; Ramona Lopez; Madhavi Sriram; Benson L. Nguyen; John J. Hall; Raymond J. Kessler; Anupama Shirali; Li Liu; Charles M. Garner; George R. Pettit; Ernest Hamel; David J. Chaplin; Ralph P. Mason; Mary Lynn Trawick; Kevin G. Pinney
The natural products colchicine and combretastatin A-4 are potent inhibitors of tubulin assembly, and they have inspired the design and synthesis of a large number of small-molecule, potential anticancer agents. The indole-based molecular scaffold is prominent among these SAR modifications, leading to a rapidly increasing number of agents. The water-soluble phosphate prodrug 33 (OXi8007) of 2-aryl-3-aroylindole-based phenol 8 (OXi8006) was prepared by chemical synthesis and found to be strongly cytotoxic against selected human cancer cell lines (GI₅₀ = 36 nM against DU-145 cells, for example). The free phenol, 8 (OXi8006), was a strong inhibitor (IC₅₀ = 1.1 μM) of tubulin assembly. The corresponding phosphate prodrug 33 (OXi8007) also demonstrated pronounced interference with tumor vasculature in a preliminary in vivo study utilizing a SCID mouse model bearing an orthotopic PC-3 (prostate) tumor as imaged by color Doppler ultrasound. The combination of these results provides evidence that the indole-based phosphate prodrug 33 (OXi8007) functions as a vascular disrupting agent that may prove useful for the treatment of cancer.
Bioorganic & Medicinal Chemistry | 2013
Rajendra P. Tanpure; Clinton S. George; Tracy E. Strecker; Laxman Devkota; Justin K. Tidmore; Chen-Ming Lin; Christine A. Herdman; Matthew T. MacDonough; Madhavi Sriram; David J. Chaplin; Mary Lynn Trawick; Kevin G. Pinney
Diversely functionalized, fused aryl-alkyl ring systems hold a prominent position as well-established molecular frameworks for a variety of anti-cancer agents. The benzosuberene (6,7 fused, also referred to as dihydro-5H-benzo[7]annulene and benzocycloheptene) ring system has emerged as a valuable molecular core component for the development of inhibitors of tubulin assembly, which function as antiproliferative anti-cancer agents and, in certain cases, as vascular disrupting agents (VDAs). Both a phenolic-based analogue (known as KGP18, compound 39) and its corresponding amine-based congener (referred to as KGP156, compound 45), which demonstrate strong inhibition of tubulin assembly (low micromolar range) and potent cytotoxicity (picomolar range for KGP18 and nanomolar range for KGP156) are noteworthy examples of such benzosuberene-based compounds. In order to extend the structure-activity relationship (SAR) knowledge base related to benzosuberene anti-cancer agents, a series of eleven analogues (including KGP18) were prepared in which the methoxylation pattern on the pendant aryl ring as well as functional group incorporation on the fused aryl ring were varied. The synthetic approach to these compounds featured a sequential Wittig olefination, reduction, Eatons reagent-mediated cyclization strategy to achieve the core benzosuberone intermediate, and represented a higher-yielding synthesis of KGP18 (which we prepared previously through a ring-expansion strategy). Incorporation of a fluorine or chlorine atom at the 1-position of the fused aryl ring or replacement of one of the methoxy groups with hydrogen (on the pendant aryl ring of KGP18) led to benzosuberene analogues that were both strongly inhibitory against tubulin assembly (IC50 approximately 1.0 μM) and strongly cytotoxic against selected human cancer cell lines (for example, GI50=5.47 nM against NCI-H460 cells with fluoro-benzosuberene analogue 37). A water-soluble phosphate prodrug salt of KGP18 (referred to as KGP265, compound 44) and a water-soluble serinamide salt (compound 48) of KGP156 were also synthesized and evaluated in this study.
Bioorganic & Medicinal Chemistry Letters | 2008
John J. Hall; Madhavi Sriram; Tracy E. Strecker; Justin K. Tidmore; Christopher J. Jelinek; G.D. Kishore Kumar; Mallinath B. Hadimani; George R. Pettit; David J. Chaplin; Mary Lynn Trawick; Kevin G. Pinney
Journal of Natural Products | 2009
Anupama Shirali; Madhavi Sriram; John J. Hall; Benson L. Nguyen; Rajsekhar Guddneppanavar; Mallinath B. Hadimani; J. Freeland Ackley; Rogelio Siles; Christopher J. Jelinek; Phyllis Arthasery; Rodney C. Brown; Victor L. Murrell; Austin McMordie; Suman Sharma; David J. Chaplin; Kevin G. Pinney
MedChemComm | 2012
Rajendra P. Tanpure; Clinton S. George; Madhavi Sriram; Tracy E. Strecker; Justin K. Tidmore; Ernest Hamel; Amanda K. Charlton-Sevcik; David J. Chaplin; Mary Lynn Trawick; Kevin G. Pinney
Archive | 2006
Kevin G. Pinney; Madhavi Sriram
Journal of Labelled Compounds and Radiopharmaceuticals | 2009
Rodney T. Brown; Victor L. Murrell; Austin McMordie; Madhavi Sriram; Kevin G. Pinney; Suman Sharma; David J. Chaplin
Archive | 2011
Kevin G. Pinney; Madhavi Sriram; Clinton S. George; Rajendra P. Tanpure
MedChemComm | 2018
Casey J. Maguire; Zhi Chen; Vani P. Mocharla; Madhavi Sriram; Tracy E. Strecker; Ernest Hamel; Heling Zhou; Ramona Lopez; Yifan Wang; Ralph P. Mason; David J. Chaplin; Mary Lynn Trawick; Kevin G. Pinney