2. Academic Validation
  3. Synthesis of cyclic 1,9-acetal derivatives of forskolin and their bioactivity evaluation

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

  • Eur J Med Chem. 2014 Nov 24:87:735-44. doi: 10.1016/j.ejmech.2014.10.013.
Devendar Ponnam 1,  Singh Shilpi 2,  K V N S Srinivas 3,  Luqman Suiab 2,  Sarfaraz Alam 4,  Zehra Amtul 5,  Niranjan Kumar Arigari 1,  Kotesh Kumar Jonnala 6,  Lubna Siddiqui 2,  Vijaya Dubey 2,  Ashok Kumar Tiwari 5,  Sridhar Balasubramanian 7,  Feroz Khan 4
Affiliations

Affiliations

  • 1 Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants- Research Centre, Boduppal, Hyderabad 500092, Telangana, India.
  • 2 Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Kukrail Picnic Spot Road, Lucknow 226015, UP, India.
  • 3 Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants- Research Centre, Boduppal, Hyderabad 500092, Telangana, India. Electronic address: kvnssrinivas@yahoo.co.in.
  • 4 Metabolic & Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Kukrail Picnic Spot Road, Lucknow 226015, UP, India.
  • 5 Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, Telangana, India.
  • 6 Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants- Research Centre, Boduppal, Hyderabad 500092, Telangana, India. Electronic address: koteshkumarj@yahoo.com.
  • 7 CSIR-Centre for X-ray Crystallography, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, Telangana, India.
PMID: 25305717 DOI: 10.1016/j.ejmech.2014.10.013
Abstract

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.

Keywords

Acetal derivatives; Anticancer activity; Ceric ammonium nitrate; Forskolin; α-Glucosidase activity.

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