Korrapati Suresh Babu

Sulfamic acid promoted one-pot three-component synthesis and cytotoxic evaluation of spirooxindoles

A simple, mild and efficient method for the synthesis of pyrazolopyridine based spirooxindoles by the three-component reaction has been developed using sulfamic acid (H2NSO3H) as a green catalyst. The method involves use of water as a solvent which makes it eco-friendly. The catalyst used is readily available and is prominent for short reaction time, operational simplicity and high yields. After completion of the reaction the catalyst could be recovered and reused for up to four cycles without loss in catalytic activity. Employing this method a library of 34 compounds has been synthesized and investigated for their cytotoxicity against a panel of three human cancer cell lines. Some of the compounds like 4o and 4p exhibited remarkable cytotoxicities with IC50 values of 0.35μM and 1.92μM against MDA-MB-231 cell line.

L-Proline mediated synthesis of quinoxalines; evaluation of cytotoxic and antimicrobial activity

A simple, greener and highly efficient method for the synthesis of functionalized quinoxalines has been developed employing L-proline as a catalyst in water. To the best of our knowledge this transformation is achieved for the first time using an organic catalyst. A small library of quinoxaline–sulphonamide conjugates have been synthesized using this protocol. The newly synthesized conjugates have been tested for their cytotoxicity and antimicrobial activity against several bacterial strains including one fungal strain. The majority of the compounds have exhibited significant cytotoxicity as well as antimicrobial activity. Compounds 5a, 5b and 5d were found to be promising with respect to both cytotoxicity and antimicrobial activity.

Combretastatin linked 1,3,4-oxadiazole conjugates as a Potent Tubulin Polymerization inhibitors

A new class of combretastatin linked 1,3,4-oxadiazoles were designed, synthesized and screened for their cytotoxic activity against five human cancer cell lines such as HeLa, DU-145, A549, MDA-MB-231 and B16. These compounds showed significant cytotoxicity with IC50 values in the range 0.118-54.32μM. Conjugate 5m displayed potent antiproliferative activity against DU-145 cell line. Flow cytometric analysis revealed that these compounds arrested the cell cycle in G2/M phase. Moreover, the tubulin polymerization assay and immunofluorescence analysis indicate that 5m exhibits potent inhibitory effect on the tubulin assembly. Further, DNA fragmentation and Hoecst staining assays confirm that 5m induces apoptosis. Molecular docking studies and competitive binding assay indicated that 5m effectively bind at the colchicine binding site of the tubulin.

Synthesis and biological evaluation of 1,2,3‐triazole tethered pyrazoline and chalcone derivatives

A series of pyrazoline derivatives and corresponding chalcone intermediates with substituents same as combretastatin‐A4(CA‐4) conjugated with triazole nucleus has been synthesized and evaluated for their anticancer potential. Sulphorhodamine B(SRB) assay indicated compound 12c to be the most active compound from the series with GI50 value of 6.7 μm against the human liver carcinoma cell line HepG2. Interestingly, the intermediate 11c exhibited more promising cytotoxicity demonstrating GI50 value of 1.3 μm against the prostate cancer cell line DU145. Compounds 11c and 12c caused accumulation of cells in G2/M phase and inhibited tubulin polymerization. Furthermore, these compounds reduce the mitochondrial membrane potential and activate caspases 3 and 9, thereby indicating their ability to trigger apoptosis.

Sulfamic acid catalyzed one-pot, three-component green approach: synthesis and cytotoxic evaluation of pyrazolyl-thiazole congeners

An efficient, operationally simple and one-pot multi-component approach has been developed for the construction of pyrazolyl-thiazoles using sulfamic acid (H2NSO3H) as a green catalyst in water. The notable features of this protocol include mild reaction conditions, enhanced selectivity with good yields and wide substrate scope, which makes it an attractive and useful process for the synthesis of biologically important newer pyrazolyl-thiazole compounds. A series of compounds (4a–z) were synthesized and also evaluated for their cytotoxic activity against three human cancer cell lines. Among them, 4b, 4c and 4e exhibited considerable cytotoxicity with an IC50 value of < 5 μM.

Biological evaluation of 3-hydroxybenzyl alcohol, an extrolite produced by Aspergillus nidulans strain KZR-132

The aim of the study was to purify and characterize a bioactive compound from Aspergillus nidulans strain KZR‐132 and its biological evaluation.

2-Anilino-3-Aroylquinolines as Potent Tubulin Polymerization Inhibitors

Several 2‐anilino‐3‐aroylquinolines were designed, synthesized, and screened for their cytotoxic activity against five human cancer cell lines: HeLa, DU‐145, A549, MDA‐MB‐231, and MCF‐7. Their IC50 values ranged from 0.77 to 23.6 μm. Among the series, compounds 7 f [(4‐fluorophenyl)(2‐((4‐fluorophenyl)amino)quinolin‐3‐yl)methanone] and 7 g [(4‐chlorophenyl)(2‐((4‐fluorophenyl)amino)quinolin‐3‐yl)methanone] showed remarkable antiproliferative activity against human lung cancer and prostate cancer cell lines. The IC50 values for inhibiting tubulin polymerization were 2.24 and 2.10 μm for compounds 7 f and 7 g, respectively, and were much lower than that of the reference compound E7010 [N‐(2‐(4‐hydroxyphenylamino)pyridin‐3‐yl)‐4‐methoxybenzenesulfonamide]. Furthermore, flow cytometric analysis revealed that these compounds arrest the cell cycle at the G2/M phase, leading to apoptosis. Apoptosis was also confirmed by mitochondrial membrane potential, Annexin V–FITC assay, and intracellular ROS generation. Immunohistochemistry, western blot, and tubulin polymerization assays showed that these compounds disrupt tubulin polymerization. Molecular docking studies revealed that these compounds bind efficiently to β‐tubulin at the colchicine binding site.