TY - JOUR
T1 - Synthesis and Characterization of Griseofulvin Derivatives as Microtubule-Stabilizing Agents
AU - Firdous, Farhat
AU - Ibrahim, Rida
AU - Furqan, Muhammad
AU - Khan, Hina
AU - Raza, Hadeeqa
AU - Singh, Upendra
AU - Emwas, Abdul Hamid
AU - Jaremko, Mariusz
AU - Chotana, Ghayoor Abbas
AU - Faisal, Amir
AU - Saleem, Rahman Shah Zaib
N1 - Funding Information:
. RSZS acknowledges Higher Education Commission, Pakistan (NRPU‐5914) and LUMS Faculty Initiative Funds (FIF‐533)
Publisher Copyright:
© 2022 Wiley-VCH GmbH.
PY - 2022/11/18
Y1 - 2022/11/18
N2 - Microtubules have been an attractive target of cancer drug discovery due to their highly dynamic nature during mitosis. Griseofulvin, a natural antifungal compound, is known to interfere with microtubule dynamics. In the present study, we prepared and analyzed twenty-seven novel griseofulvin derivatives. Three of these compounds had GI50 values <10 μM (5.74 to 9.7 μM) in breast cancer cell line CAL-51. The most promising compound ((2S,6’R)-4’-(benzhydrylamino)-7-chloro-4,6-dimethoxy-6’-methyl-3H-spiro[benzofuran-2,1’-cyclohexan]-3’-ene-2’,3-dione), was characterized as a microtubule-stabilizing agent with a GI50 value of 5.74±1.43 μM compared to 10.79±3.06 μM GI50 for parental griseofulvin. It also inhibited the proliferation of other cancer cell lines, including KB-3-1 and HCT116, with GI50 values of 1.19±0.34 μM and 2.48±0.40 μM, respectively. Treatment of cancer cells with it resulted in aberrant mitosis causing G2/M arrest. Finally, we show that this compound increased the expression of p53 protein and induced apoptotic cell death.
AB - Microtubules have been an attractive target of cancer drug discovery due to their highly dynamic nature during mitosis. Griseofulvin, a natural antifungal compound, is known to interfere with microtubule dynamics. In the present study, we prepared and analyzed twenty-seven novel griseofulvin derivatives. Three of these compounds had GI50 values <10 μM (5.74 to 9.7 μM) in breast cancer cell line CAL-51. The most promising compound ((2S,6’R)-4’-(benzhydrylamino)-7-chloro-4,6-dimethoxy-6’-methyl-3H-spiro[benzofuran-2,1’-cyclohexan]-3’-ene-2’,3-dione), was characterized as a microtubule-stabilizing agent with a GI50 value of 5.74±1.43 μM compared to 10.79±3.06 μM GI50 for parental griseofulvin. It also inhibited the proliferation of other cancer cell lines, including KB-3-1 and HCT116, with GI50 values of 1.19±0.34 μM and 2.48±0.40 μM, respectively. Treatment of cancer cells with it resulted in aberrant mitosis causing G2/M arrest. Finally, we show that this compound increased the expression of p53 protein and induced apoptotic cell death.
KW - Apoptosis
KW - Cancer
KW - Cell cycle arrest
KW - Griseofulvin
KW - Microtubule stabilizing agents
KW - Tubulin polymerization
UR - http://www.scopus.com/inward/record.url?scp=85142369486&partnerID=8YFLogxK
U2 - 10.1002/slct.202202832
DO - 10.1002/slct.202202832
M3 - Article
AN - SCOPUS:85142369486
SN - 2365-6549
VL - 7
JO - ChemistrySelect
JF - ChemistrySelect
IS - 43
M1 - e202202832
ER -
