title: Synthesis of cyclic 1,9-acetal derivatives of forskolin and their bioactivity evaluation.
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.
authors.affiliation: Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants- Research Centre, Boduppal, Hyderabad 500092, Telangana, India.
authors.forename: Devendar
authors.initials: D
authors.lastname: Ponnam
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Kukrail Picnic Spot Road, Lucknow 226015, UP, India.
authors.forename: Singh
authors.initials: S
authors.lastname: Shilpi
authors.affiliation: Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants- Research Centre, Boduppal, Hyderabad 500092, Telangana, India. Electronic address: kvnssrinivas@yahoo.co.in.
authors.forename: K V N S
authors.initials: KV
authors.lastname: Srinivas
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Kukrail Picnic Spot Road, Lucknow 226015, UP, India.
authors.forename: Luqman
authors.initials: L
authors.lastname: Suiab
authors.affiliation: Metabolic & Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Kukrail Picnic Spot Road, Lucknow 226015, UP, India.
authors.forename: Sarfaraz
authors.initials: S
authors.lastname: Alam
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, Telangana, India.
authors.forename: Zehra
authors.initials: Z
authors.lastname: Amtul
authors.affiliation: Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants- Research Centre, Boduppal, Hyderabad 500092, Telangana, India.
authors.forename: Niranjan Kumar
authors.initials: NK
authors.lastname: Arigari
authors.affiliation: Natural Product Chemistry, CSIR-Central Institute of Medicinal and Aromatic Plants- Research Centre, Boduppal, Hyderabad 500092, Telangana, India. Electronic address: koteshkumarj@yahoo.com.
authors.forename: Kotesh Kumar
authors.initials: KK
authors.lastname: Jonnala
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Kukrail Picnic Spot Road, Lucknow 226015, UP, India.
authors.forename: Lubna
authors.initials: L
authors.lastname: Siddiqui
authors.affiliation: Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Kukrail Picnic Spot Road, Lucknow 226015, UP, India.
authors.forename: Vijaya
authors.initials: V
authors.lastname: Dubey
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, Telangana, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Tiwari
authors.affiliation: CSIR-Centre for X-ray Crystallography, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, Telangana, India.
authors.forename: Sridhar
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Metabolic & Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Kukrail Picnic Spot Road, Lucknow 226015, UP, India.
authors.forename: Feroz
authors.initials: F
authors.lastname: Khan
mesh_terms: D000080:Acetals / Q000737:chemistry*; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D005576:Colforsin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D006801:Humans; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000080:Acetals; D005576:Colforsin
keywords: Acetal derivatives; Anticancer activity; Ceric ammonium nitrate; Forskolin; α-Glucosidase activity