Conjugate of podophyllotoxin with chlorambucil: synthesis, biological testing and molecular modeling
نویسندگان
چکیده
In the present work we have studied a novel conjugate of DNA alkylating agent chlorambucil with podophyllotoxin, ligand colchicine binding site in tubulin. The target compound was obtained by Steglich esterification podophyllotoxin percentage yield 41%. Results biotesting carried out on carcinoma A549 cell line revealed that at concentration 2 μM caused full depolymerization microtubules without any other effect free inhibited proliferation (IC50=135±30 nM) and growth (EC50=240±30 cells. data computer molecular docking into 3D model α,β-tubulin dynamics modelling allowed to explain observed difference effects chlorambucil-podophyllotoxin chlorambucil-colchicine conjugates microtubules.
منابع مشابه
synthesis and characterization of potentially biological active cyclometallated organoplatinum(ii) complexes
this work is presented in five parts. in the first part preparation of the starting complex [pt(c^n)cl(dmso)], 1, in which c^n = n(1),c(2?)-chelated, deprotonated 2-phenylpyridine, and dmso = dimethylsulfoxide, and its reaction with 1 equiv of the biphosphine ligands bis(diphenylphosphino)amine, dppa, or bis(diphenylphosphino)methane, dppm, to give the complex [pt(c^n)cl(dppa)], 2, or [pt(c^n)c...
15 صفحه اولSynthesis, biological and molecular modeling studies of macrocyclic complexes of trivalent metal ions
The macrocyclic complexes of biological importance with power transition metals are synthesized by template methodology leading to the formation of the complex [MLX] X2; where L is macrocyclic ligand derived from 3,4-diaminotoluene, 2,4-thiazolidinedione, M=Cr (III) and Fe(III) X is Cl-, CH3COO- or NO3_.Characterisation of these complexes are through with the assistance of elemental analyses(CH...
متن کاملSynthesis and evaluation of biological properties of ferrocenyl-podophyllotoxin conjugates.
Three types, esters, amides and 1,2,3-triazoles, of ferrocenyl-podophyllotoxin conjugates were synthesised, and their anticancer activity was evaluated. We observed that the most potent ferrocenyl derivatives were esters. Esters 15, 16 and 17 acted in a similar way to podophyllotoxin, i.e. reduced the number of G1 phase cells and induced G2/M blockage, while esters 14 and 18 and amide 19 blocke...
متن کاملAmino and chlorambucil analogues of pentamidine--synthesis and biological examinations.
The amino analogues of pentamidine with a polymethylene (n = 3 - 6) chain and their chlorambucil derivatives were synthesized. The obtained compounds revealed cytotoxic effect on MCF-7 human breast cancer cell line (IC50 = 22 - 95 +/- 2 pM), mainly by the induction of apoptosis. The topoisomerase I/II inhibition assay and the ethidium displacement assay with the use of pBR322 plasmid DNA were u...
متن کاملsingle-step synthesis of multi-component spirobarbiturates using ionic liquids and synthesis of substituted pyridine filled with catalysts supported on solid substrate
in this thesis, a better reaction conditions for the synthesis of spirobarbiturates catalyzed by task-specific ionic liquid (2-hydroxy-n-(2-hydroxyethyl)-n,n-dimethylethanaminium formate), calcium hypochlorite ca(ocl)2 or n-bromosuccinimide (nbs) in the presence of water at room temperature by ultrasonic technique is provided. the design and synthesis of spirocycles is a challenging task becaus...
15 صفحه اولذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Biomeditsinskaia khimiia
سال: 2021
ISSN: ['2310-6905', '2310-6972']
DOI: https://doi.org/10.18097/pbmc20216703289