• RADHIKA T. Department of Pharmaceutical Chemistry, G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad 500028, India,
  • SAISREE K. Department of Pharmacy, OUCT, Osmania University, Hyderabad. India
  • HARINADHA BABU V. Department of Pharmacy, OUCT, Osmania University, Hyderabad. India



BromoIsatin, Isoxazole hydrazides, Molecular Docking, VEGFR-2 Kinase enzyme assay, invitro antiproliferative assay, ADMET study


Objective: To design, synthesize, in vitro Vascular Endothelial Growth Factor Receptor (VEGFR-2) assay, antiproliferative activity an Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) studies of some novel bromoisatin incorporated isoxazole derivatives.

Methods: Designed compounds were synthesized by the condensation of different 3-aryl-5-methylisoxazole-4-carbohydrazides (5a-h) with 5-bromoisatin to give the target molecules. To predict the affinity and activity of the ligand molecule the docking program GOLD 3.1 was employed to generate different bioactive binding poses of designing molecules at the active site of protein VEGFR-2. All the synthesized compounds were characterized based on the spectral and elemental analysis data. Antiproliferative activity performed against Human Umbilical vein endothelial cells (HUVEC cell line).

Results: All the synthesized compounds showed the characteristic peaks in FTIR,1H, C[13]NMR and Mass spectral analysis. In molecular docking, all the synthesized compounds (6a-j) exhibited high fitness scores with minimum three bonding interaction with the active site VEGFR-2 kinase. In in-vitro, VEGFR-2 kinase assay, compounds 6a, 6b, 6d and 6e exhibited more than 70% inhibition at a single dose concentration of 5μM. In antiproliferative assay against HUVEC cell lines, compounds 6d and 6e exhibited potent activity with IC50 values in nanomolar concentrations. ADMET results of 6a, 6b, 6d and 6e are quite promising with least hepatotoxicity and good bioavailability.

Conclusion: The derivatives were synthesized in quantitative yields. New derivatives posses antiproliferative activity, least hepatotoxicity and good bioavailability.


Download data is not yet available.

Author Biography

RADHIKA T., Department of Pharmaceutical Chemistry, G. Pulla Reddy College of Pharmacy, Osmania University, Hyderabad 500028, India,

Pharmaceutical chemistry


Kamal A, Reddy JS, Ramaiah MJ, Dastagiri D, Bharathi EV, Azhar MA, et al. Design, synthesis and biological evaluation of 3, 5-diaryl-isoxazoline/isoxazole-pyrrolobenzodiazepine conjugates as potential anticancer agents. Eur J Med Chem 2010;45:3924-37.

Rajanarendar E, Reddy MN, Krishna SR, Reddy KG, Reddy YN, Rajam MV. Design, synthesis, in vitro antimicrobial and anticancer activity of novel methylenebis-isoxazolo [4, 5-b] azepines derivatives. Eur J Med Chem 2012;50:344-9.

Radhika T, Sravanthi S, Babu VH, Reddy BM. Synthesis, biological evaluation and molecular docking studies of isoxazole synchronized quinazolinone derivatives. J Pharm Res 2017;11:895-2.

Edafiogho IO, Hinko CN, Chang H, Moore JA, Mulzac D, Nicholson JM, et al. Synthesis and anticonvulsant activity of enaminones. J Med Chem 1992;35:2798-5.

Chikkula KSR. Isoxazole –A potent pharmacophore. Int J Pharm Pharma Sci 2017;9:13-4.

Yang Z, Li P, Gan X. Novel pyrazole-hydrazone derivatives containing an isoxazole moiety: design, synthesis, and antiviral activity. Mol 2018;23:1798.

Kalirajan R, Rafick MH, Sankar S, Jubie S. Docking studies, synthesis, characterization and evaluation of their antioxidant and cytotoxic activities of some novel isoxazole-substituted 9-anilinoacridine derivatives. Sci World J 2012;2012:165258.

Kumar A, Maurya RA, Sharma S, Ahmad P, Singh AB, Tamrakar AK, et al. Design and synthesis of 3, 5-diarylisoxazole derivatives as novel class of anti-hyperglycemic and lipid lowering agents. Bio Med Chem 2009;17:5285-92.

Basha SS, Divya K, Padmaja A, Padmavathi V. Synthesis and antimicrobial activity of thiazolyl pyrazoles and isoxazoles. Res Chem Int 2015;41:10067-83.

Meenakshi K, Gopal N, Sarangapani M. Synthesis, characterization and antimicrobial activity of some novel schiff and mannich bases of isatin. Int J Pharm Pharm Sci 2014;6:318-22.

Debnath B, Ganguly S. Molecular docking studies and ADME prediction of novel isatin analogs as hiv-1-rt inhibitors with broad spectrum chemo therapeutic properties. Asian J Pharm Clin Res 2014;7:186-9.

Smitha S, Pandeya S, Stables J, Ganapathy S. Anticonvulsant and sedative-hypnotic activities of N-acetyl/methyl isatin derivatives. Sci Pharm 2008;76:621-36.

El-Faham A, Farooq M, Khattab SN, Abutaha N, Wadaan MA, Ghabbour HA, et al. Synthesis, characterization, and anti-cancer activity of some new N′-(2-Oxoindolin-3-ylidene)-2-propylpentane hydrazide-hydrazones derivatives. Mole 2015;13:14638-55.

Chandra PM, Venkateshwar J. Biological evaluation of schiff bases of new isatin derivatives for anti alzheimer’s activity. Asian J Pharm Clin Res 2014;7:114-7.

Hoff PM, Wolff RA, Bogaard K, Waldrum S, Abbruzzese JL. A phase I study of escalating doses of the tyrosine kinase inhibitor semaxanib (SU5416) in combination with irinotecan in patients with advanced colorectal carcinoma. Japan J Clin Oncol 2006;1:100-3.

Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti-and pro-angiogenic therapies. Gen Canc 2011;2:1097-5.

SB B, Adhikari S, Surana SJ. Tyrosine kinase receptor inhibitors: A new target for anticancer drug development. J Pharma Sci Tech 2012;1:36-45.

Li Z, Wang B, Tang L, Chen S, Li J. Quinazoline derivative compound (11d) as a novel angiogenesis inhibitor inhibiting VEGFR-2 and blocking VEGFR2-mediated Akt/mTOR/p70s6k signaling pathway. Iran J B Med Scien 2016;19:411.

Corbacho AM, Macotela Y, Nava G, Torner L, Duenas Z, Noris G, et al. Human umbilical vein endothelial cells express multiple prolactin isoforms. J End 2000;166:53-62.

Haddad JJ. The immunopharmacologic potential of Semaxanib and new generation directed therapeutic drugs: receptor tyrosine kinase regulation with anti-tumorigenensis/angiogenesis properties. Sau Pharma J 2012;30:103-23.



How to Cite

T., R., S. . K., and H. B. . V. “DESIGN, DOCKING AND SYNTHESIS OF NOVEL BROMO ISATIN INCORPORATED ISOXAZOLE DERIVATIVES AS VEGFR-2 INHIBITORS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 11, no. 4, Apr. 2019, pp. 1-7, doi:10.22159/ijpps.2019v11i4.31933.



Original Article(s)