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
  • 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: [email protected].
  • 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: [email protected].
  • 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.