Synthesis of neolignans as microtubule stabilisers.
Tubulin is a well established target for anticancer drug development. Lignans and neolignans were synthesized as tubulin interacting agents. Neolignans 10 and 19 exhibited significant anticancer activity against MCF-7 and MDAMB-231 human breast cancer cell lines. Both the compounds effectively induced stabilization of microtubule at 4 and 20 μM concentrations respectively. Neolignan 10 induced G2/M phase arrest in MCF-7 cells. Docking experiments raveled that 10 and 19 occupied the same binding pocket of paclitaxel with some difference in active site amino acids and good bioavailability of both the compounds. In in vivo acute oral toxicity 10 was well tolerated up to 300 mg/kg dose in Swiss-albino mice.
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
B
B
Sathish Kumar
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
Aastha
A
Singh
CSIR-Central Drug Research Institute (CSIR-CDRI), B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Amit
A
Kumar
CSIR-Central Drug Research Institute (CSIR-CDRI), B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Jyotsna
J
Singh
CSIR-Central Drug Research Institute (CSIR-CDRI), B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Mohammad
M
Hasanain
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
Arjun
A
Singh
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
Nusrat
N
Masood
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
Dharmendra K
DK
Yadav
CSIR-Central Drug Research Institute (CSIR-CDRI), B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Rituraj
R
Konwar
CSIR-Central Drug Research Institute (CSIR-CDRI), B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Kalyan
K
Mitra
CSIR-Central Drug Research Institute (CSIR-CDRI), B.S. 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
Jayanta
J
Sarkar
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
Suaib
S
Luqman
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
Anirban
A
Pal
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
Feroz
F
Khan
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India.
Debabrata
D
Chanda
CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP), Kukrail Picnic Spot Road, P.O. CIMAP, Lucknow 226015, India. Electronic address: arvindcimap@rediffmail.com.
Arvind S
AS
Negi
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D001835:Body Weight / Q000187:drug effects; D045744:Cell Line, Tumor; D003373:Coumaric Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D017705:Lignans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000737:chemistry* / Q000378:metabolism
D000970:Antineoplastic Agents; D003373:Coumaric Acids; D017705:Lignans; D014404:Tubulin; C000591907:diethyl 4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate; C000591908:diethyl 4-acetoxy-4'-hydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate
Acute oral toxicity; Anticancer; In silico studies; Lignans; Microtubules; Neolignans