Sridhar Balasubramanian

Eco-friendly synthesis and biological evaluation of substituted pyrano[2,3-c]pyrazoles

An ecofriendly green approach for synthesis of substituted pyrano[2,3-c]pyrazoles has been developed via a multicomponent one pot approach in aqueous ethanol medium under totally non-catalytic conditions. The synthesized compounds were evaluated for their antibacterial, anti-inflammatory and cytotoxic activities.

Macrocyclic Glycohybrid Toolbox Identifies Novel Antiangiogenesis Agents from Zebrafish Assay

A practical and modular approach to obtain a diverse set of 14-membered macrocyclic compounds from carbohydrates is developed that utilizes functional groups at C-1 and C-5. The evaluation of this toolbox in various zebrafish assays led to the identification of 2.7f as an antiangiogenesis agent.

14-Membered Macrocyclic Ring-Derived Toolbox: The Identification of Small Molecule Inhibitors of Angiogenesis and Early Embryo Development in Zebrafish Assay

A highly practical and modular synthesis to obtain a diverse 14-membered ring-based macrocyclic toolbox is achieved. These compounds were further tested in zebrafish assays related to early embryonic development, angiogenesis, and neurogenesis, respectively. 1.4c was identified as an antiangiogenesis agent.

Synthesis, in vitro anticancer and antimycobacterial evaluation of new 5-(2,5-dimethoxyphenyl)-1,3,4-thiadiazole-2-amino derivatives

A series of 2,5-disubstituted-1,3,4-thiadiazole derivatives 5a-5l, 7a-7e and 9 have been synthesised and screened for in vitro antimycobacterial activity against Mycobacterium smegmatis MC-155. In addition these compounds have also been screened for cytotoxic activity against cancer cell lines HT-29, MDA-MB-231 by MTT colorimetric assay. The compounds are well characterized by spectral analysis viz. (1)H NMR, (13)C NMR, FT-IR, mass and HRMS. Screening results indicate that compounds 5g, 7a possess good antitubercular activity with MIC value 65.74 and 40.86, respectively, compounds 5g, 7a, 7b, 7d, 7e and 9 displayed promising cytotoxic activity against the cell lines tested. 5g and 7a stand out to be potent antimycobacterial and anticancer agents among the tested series. Further the title compounds were also tested on human normal cells HEK293T and are found to be safer with lesser cytotoxicity. It is interesting to observe that compound 5g has come out to be safer, potent anticancer and antimycobacterial agent.

Synthesis, antimicrobial activity and molecular docking of novel tetracyclic scaffolds incorporating a flavonoid framework with medium sized oxygen heterocycles.

A convenient approach for the synthesis of novel tetracyclic scaffolds incorporating a flavonoid framework with medium sized heterocyclic rings (eight-, nine-, ten- and eleven-membered rings) containing two oxygen atoms from flavonols through alkylation using different dibromoalkanes was described. The synthesized compounds were established based on the spectral data and X-ray crystal structure for 6c. The synthesized compounds were evaluated for their in vitro antimicrobial activity. Docking studies were carried out for most active two compounds 6f and 6i.

Synthesis of cyclic 1,9-acetal derivatives of forskolin and their bioactivity evaluation.

A new series of 1,9-acetals of forskolin were synthesized by treating with aromatic and aliphatic aldehydes using Ceric ammonium nitrate as catalyst and evaluated for anticancer and α-glucosidase inhibition activities. Among the synthesized compounds 2a, 2b and 3a showed potential cytotoxic activity towards human cancer cell lines MCF-7 (Human Breast Adenocarcinoma), MDA-MB (Human Breast Carcinoma), HeLa (Human Cervix Adenocarcinoma), A498 (Human Kidney Carcinoma), K562 (Human Erythromyeloblastoid leukemia), SH-SY5Y (Human Neuroblastoma), Hek293 (Human Embryonic Kidney) and WRL68 (Human Hepatic) with IC50 values ranging between 0.95 and 47.96 μg/ml. Osmotic fragility test revealed compound 3a as non-toxic to human erythrocytes at the tested concentrations of 50 and 100 μg/ml. Compounds 1g (IC50 value 0.76 μg/ml) and 1p (IC50 value 0.74 μg/ml) significantly inhibited α-glucosidase in in vitro system. In silico based docking, ADME and toxicity risk assessment studies also showed discernible α-glucosidase activity for compounds 1g, 1p compared to standard acarbose.

I2-Catalyzed Oxidative N–S Bond Formation: Metal-Free Regiospecific Synthesis of N-Fused and 3,4-Disubstituted 5-Imino-1,2,4-thiadiazoles

A novel and expeditious approach for the synthesis of N-fused and 3,4-disubstituted 5-imino-1,2,4-thiadiazole derivatives has been achieved through the molecular iodine-catalyzed oxidative cyclization of 2-aminopyridine/amidine and isothiocyanate via N-S bond formation at ambient temperature. The present one-pot transition-metal-free protocol provides the facile and highly efficient regiospecific synthesis of various 1,2,4-thiadiazole derivatives in a scaled-up manner with good to excellent yields using inexpensive I2 as a catalyst.

Synthesis, molecular properties prediction and anticancer, antioxidant evaluation of new edaravone derivatives.

A series of new edaravone derivatives 3-7 have been synthesized, characterised using various spectroscopic techniques and screened for their in vitro anti-cancer, antioxidant activities. Structure of 5d was further substantiated through single crystal X-ray diffraction. Among the tested, 5l exhibited pronounced activity against PC3 cancer cells. Compounds 5i, 5l, 7c showed potent activity against A549 cancer cells. Products 5k, 6, 7c demonstrated good antioxidant activity with MIC values of 18.60, 16.27, 16.07μg/mL respectively. Further the reported analogues were also tested on normal HEK293T cells and displayed low to good safer profiles. Derivatives 5l and 7c have come out to be safer potent anticancer, antioxidant agents. Additionally, the target products were subjected to their molecular properties prediction and drug likeness by employing Molinspiration and Osiris property explorer toolkits. None of them violated Lipinskis boundaries classifying the title compounds as potential anticancer and antioxidant agents.

Sequential C–N and C–O Bond Formation in a Single Pot: Synthesis of 2H-Benzo[b][1,4]oxazines from 2,5-Dihydroxybenzaldehyde and Amino acid Precursors

Functionalized β-aryl alanine ester derivatives were found to undergo rapid C-N and C-O bond formation with quinol carbonyl compounds to afford 2H-benzo[b][1,4]oxazines in good to excellent yields. This unprecedented finding reported herein offers a straightforward, highly efficient, and rapid method for the synthesis of 2H-benzo[b][1,4]oxazines.

Bis-spirochromanones as potent inhibitors of Mycobacterium tuberculosis: synthesis and biological evaluation

On the basis of reported antimycobacterial property of chroman-4-one pharmacophore, a series of chemically modified bis-spirochromanones were synthesized starting from 2-hydroxyacetophenone and 1,4-dioxaspiro[4.5] decan-8-one using a Kabbe condensation approach. The synthesized bis-spirochromanones were established based on their spectral data and X-ray crystal structure of 6e. All synthesized compounds were evaluated against Mycobacteriumtuberculosis H37Rv (ATCC 27294) strain, finding that some products exhibited good antimycobacterial activity with minimum inhibitory concentration as low as