Papers by Raed M Maklad
Journal of Enzyme Inhibition and Medicinal Chemistry
Development of 3-methyl/3-(morpholinomethyl)benzofuran derivatives as novel antitumor agents towa... more Development of 3-methyl/3-(morpholinomethyl)benzofuran derivatives as novel antitumor agents towards non-small cell lung cancer cells,
Bioorganic Chemistry , 2020
Bis-hydrazides 13a-h were designed and synthesized as potential tubulin inhibitors selectively ta... more Bis-hydrazides 13a-h were designed and synthesized as potential tubulin inhibitors selectively targeting the colchicine site between α- and β-tubulin subunits. The newly designed ring-B substituents were assisted at their ends by ‘anchor groups’ which are expected to exert binding interaction(s) with new additional amino acid residues in the colchicine site (beyond those amino acids previously reported to interact with reference inhibitors as CA-4 and colchicine). Conformational flexibility of bis-hydrazide linker assisted these ‘extra-binding’ properties through reliving ligands’ strains in the final ligand-receptor complexes. Compound 13f displayed the most promising computational and biological study results in the series: MM/GBSA binding energy of -62.362 kcal/mol (extra-binding to Arg α:221, Thr β:353 & Lys β:254); 34% NCI-H522 cells’ death (at 10 µM), IC50= 0.073 µM (MTT assay); significant cell cycle arrest at G2/M phase; 11.6% preG1 apoptosis induction and 83.1% in vitro tubulin inhibition (at concentration = IC50). Future researchers in bis-hydrazide tubulin inhibitors are advised to consider the 2-chloro-N-(4-substituted-phenyl)acetamide derivatives as compound 13f due to extra-binding properties of their ring B.
Archiv der Pharmazie, 2014
A series of novel 1‐(3,4‐methoxyphenyl)‐5‐(3,4,5‐trimethoxyphenyl)‐1H‐1,2,4‐triazole‐3‐carboxylic... more A series of novel 1‐(3,4‐methoxyphenyl)‐5‐(3,4,5‐trimethoxyphenyl)‐1H‐1,2,4‐triazole‐3‐carboxylic acid derivatives (4a–n) were synthesized and evaluated for their in vitro cytotoxic activity against the growth of four different human cell lines (hepatocarcinoma HepG2, breast adenocarcinoma MCF‐7, colon carcinoma DLD‐1, and leukemia HL‐60). The anilides of m‐anisidine 4e, o‐anisidine 4f, and 3,5‐difluoroaniline 4l demonstrated best results on MCF‐7 cells and mean IC50 values of 7.79, 10.79, and 13.20 µM, respectively. The compounds produced a significant reduction in cellular microtubules at a concentration of 25 µg/mL, for microtubule loss. Molecular modeling studies involving compounds 4d, 4e, 4f, and 4l with the colchicine binding site of α,β‐tubulin revealed hydrogen bonding and hydrophobic interactions with several amino acids in the colchicine binding site of β‐tubulin. Novel 1‐(3,4‐methoxyphenyl)‐5‐(3,4,5‐trimethoxyphenyl)‐1H‐1,2,4‐triazole‐3‐carboxylic acid derivatives (4a–n) were synthesized. With IC50 values of 7.79, 10.79, and 13.20 µM, the anilides of m‐anisidine 4e, o‐anisidine 4f, and 3,5‐difluoroaniline 4l showed best cytotoxic activity on MCF‐7 cells. In docking studies, compounds 4d, 4e, 4f, and 4l interacted with several amino acids in the colchicine binding site of β‐tubulin.
Conference Presentations by Raed M Maklad
The 43rd Annual Conferenceof Association of Egyptian-American Scholars at Zewail City of Science and Technology, 2016
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Papers by Raed M Maklad
Conference Presentations by Raed M Maklad