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From the carbolithiation of 1cyclopenta2,4dien1ylideneN,Ndimethylmethanamine =6dimethylaminofulvene; 3 and different lithiated azaindoles 21methyl7azaindol2yl, 1diethylaminomethyl7azaindol2yl, and 1methoxymethyl7azaindol2yl, the corresponding lithium cyclopentadienide intermediates 4a–4cwere formed 7azaindole=1Hpyrrolo2,3bpyridine. The latter underwent a transmetallation reaction with TiCl4resulting in the dimethylaminofunctionalised ‘titanocenes’ 5a–5c. When the ‘titanocenes’ 5a–5cwere tested against LLCPK cells, the IC50values obtained were of 8.8, 12, and 87μM, respectively. The most cytotoxic ‘titanocene’, 5a, with an IC50value of 8.8μMis nearly as cytotoxic as cisplatin, which showed an IC50value of 3.3μMwhen tested on the epithelial pig kidney LLCPK cell line, and ca.200 times better than ‘titanocene dichloride’ itself. [ABSTRACT FROM AUTHOR]

Abstract  From the carbolithiation of 6-bis-N,N-dimethylamino fulvene (3a) and different ortho-lithiated heterocycles (furan, thiophene and N-methylpyrrole), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 resulting in bis-N,N-dimethylamino-functionalised titanocenes 5a–c. When these titanocenes were tested against LLC-PK cells, the IC50-values obtained were of 240, and 270 μM for titanocenes 5b and 5c, respectively. The most cytotoxic titanocene in this paper, 5a with an IC50-value of 36 μM was found to be approximately six times less cytotoxic than its mono-N,N-dimethylamino substituted analogue Titanocene C (IC50 = 5.5 μM) and almost ten times less cytotoxic than cisplatin, which showed an IC50-value of 3.3 μM, when tested on the LLC-PK cell line. Graphical abstract  Bis-(bis- (N,N-dimethylamino)-2-(N′-methylpyrrolyl)methylcyclopentadienyl) titanium (IV) dichloride, {η5-C5H4-CH[N(CH3)2]2[C5H3NCH3]}2TiCl2 was synthesised starting from 6-bis-(N,N-dimethylamino) fulvene and 2-N-methylpyrrolyl lithium. Herein, we present the synthesis and DFT structure of the titanocene and two further derivatives followed by MTT-based cytotoxicity tests on pig kidney epithelial (LLC-PK) cells. [ABSTRACT FROM AUTHOR]

Summary  From the carbolithiation of 6-N,N-dimethylamino fulvene (3a) and different lithiated N-heterocyclic compounds (N,N-dimethylaminomethylpyrrole, 1-methylimidazole and 2,4-[bis(N′,N′-dimethylaminomethyl)]-N-methyl pyrrole), the corresponding lithium cyclopentadienide intermediate (4a–c) was formed. These three lithiated intermediates underwent a transmetallation reaction with TiCl4 resulting in dimethylamino-functionalised titanocenes 5a–c. When these titanocenes were tested against LLC-PK cells, the IC50 values obtained were of 13, and 63 μM for titanocenes 5b and 5c, respectively. The most cytotoxic titanocene in this paper (5a) with an IC50 value of 6.8 μM is found to be almost as cytotoxic as cis-platin, which showed an IC50 value of 3.3 μM, when tested on the epithelial pig kidney LLC-PK cell line, and titanocene 5c is approximately 400 times better than titanocene dichloride itself. [ABSTRACT FROM AUTHOR]

From the carbolithiation of 6-N,N-dimethylaminofulvene (3a) and different lithiated heterocycles (5-N-methylpyrazolyl, 2-thiazolyl, and 2-N(N,N-dimethylamino)methylimidazolyl), the corresponding lithium cyclopentadienide intermediate (4a−c) was formed. These three lithiated intermediates underwent a transmetalation reaction with TiCl4, resulting in dimethylamino-functionalized titanocenes 5a−c. When these titanocenes were tested against LLC-PK cells, the IC50values obtained were 53 and 61 M for titanocenes 5aand 5b, respectively. The most cytotoxic titanocene in this paper (5c), with an IC50value of 5.4 M, is found to be almost as cytotoxic as cisplatin, which showed an IC50value of 3.3 M, when tested on the epithelial pig kidney LLC-PK cell line, and titanocene 5cis approximately 400 times more active than titanocene dichloride itself. [ABSTRACT FROM AUTHOR]