title: Synthesis and biological evaluation of andrographolide analogues as anti-cancer agents.
abstract: A new family of andrographolide analogues were synthesized and screened in vitro against kidney (HEK-293) and breast (MCF-7) cancer cells. The anti-cancer effects of the active analogues (2b, 2c and 4c) were determined by multiple cell based assays such as MTT, immunostaining, FACS, western blotting and transcriptional inhibition of NF-κB activity. Importantly, these compounds were found to possess higher anti-cancer potency than andrographolide and low toxicity to normal (VERO and MCF-10A) cells. Increased level of Bax/Bcl-xL ratio, caspase 3, and sub G1 population, higher expression level of tumor suppressor protein p53 and lower expression level of NF-κB suggested potent apoptotic property of the active analogues. Data revealed that the andrographolide derivative-mediated cell death in cancer cells was p53 dependent.
authors: Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Odisha 751024, India.
authors: Ranjan
authors: R
authors: Preet
authors: Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India.
authors: Biswajit
authors: B
authors: Chakraborty
authors: Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Odisha 751024, India.
authors: Sumit
authors: S
authors: Siddharth
authors: Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Odisha 751024, India.
authors: Purusottam
authors: P
authors: Mohapatra
authors: Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Odisha 751024, India.
authors: Dipon
authors: D
authors: Das
authors: Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Odisha 751024, India.
authors: Shakti Ranjan
authors: SR
authors: Satapathy
authors: Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India.
authors: Supriya
authors: S
authors: Das
authors: Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India.
authors: Nakul C
authors: NC
authors: Maiti
authors: Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India.
authors: Prakas R
authors: PR
authors: Maulik
authors: Cancer Biology Division, KIIT School of Biotechnology, KIIT University, Campus-11, Patia, Bhubaneswar, Odisha 751024, India. Electronic address: cnkundu@gmail.com.
authors: Chanakya Nath
authors: CN
authors: Kundu
authors: Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700032, India. Electronic address: chinmay@iicb.res.in.
authors: Chinmay
authors: C
authors: Chowdhury
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D016328:NF-kappa B / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004224:Diterpenes; D016328:NF-kappa B; C030419:andrographolide; D053148:Caspase 3; D005978:Glutathione
keywords: Andrographolide; Anti-cancer; Apoptosis; C14 ester analogues; Epoxy diastereomers; HEK-293; MCF-7; Normal cells