title: Rational design, synthesis and molecular modeling studies of novel anti-oncological alkaloids against melanoma.
abstract: 3D-pharmacophore and 2D-QSAR modeling studies describe the anti-oncological properties of spiro-alkaloids. The dispiro[2H-indene-2,3'-pyrrolidine-2',3''-[3H]indole]-1,2''(1''H, 3H)-diones 20-38 were prepared via 1,3-dipolar cycloaddition reactions of azomethine ylides (generated in situ via decarboxylative condensation of isatins 7-9 with sarcosine 10) and 2-(arylmethylidene)-2,3-dihydro-1H-inden-1-ones 11-19 in refluxing ethanol. Some of the spiro-alkaloids (21, 22, 29 and 37) revealed potent antitumor properties against melanoma carcinoma cell lines (GaLa, LuPiCi and LuCa) utilizing the in vitro SRB standard method exhibiting potency close to that of the standard reference doxorubicin.
authors.affiliation: Pesticide Chemistry Department, National Research Centre, Dokki, Giza 12622, Egypt. girgisas10@yahoo.com.
authors.forename: Adel S
authors.initials: AS
authors.lastname: Girgis
authors.forename: Siva S
authors.initials: SS
authors.lastname: Panda
authors.forename: Aladdin M
authors.initials: AM
authors.lastname: Srour
authors.forename: Hanaa
authors.initials: H
authors.lastname: Farag
authors.forename: Nasser S M
authors.initials: NS
authors.lastname: Ismail
authors.forename: Mohamed
authors.initials: M
authors.lastname: Elgendy
authors.forename: Amal K
authors.initials: AK
authors.lastname: Abdel-Aziz
authors.forename: Alan R
authors.initials: AR
authors.lastname: Katritzky
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D061565:Cycloaddition Reaction; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy*; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D013141:Spiro Compounds