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Design, synthesis and in vitro cytotoxicity studies of novel pyrrolo[2,1-c][1,4]benzodiazepine (PBD) --polymade conjugates and 2,2'-PBD dimers

Reddy, B.S.; Damayanthi, Y.; Reddy, B.S.; Lown, J.W.

Anti-Cancer Drug Design 15(3): 225-238

2000

ISSN/ISBN: 0266-9536
PMID: 11049090
Document Number: 525815
A series of novel pyrrolo[2,1-c][l,4]benzodiazepine (PBD)-polyamide conjugates (1 and 2) and 2,2'-PBD dimers (3, 4 and 5) were synthesized and evaluated for cytotoxicity in >60 human tumor cell lines. In general PBD-polyamide conjugates (1 and 2) exhibit higher cytotoxic potency compared with 2,2'-PBD dimers (3, 4 and 5). Compound 2 exhibits a wide spectrum of anticancer activities against 17 cell lines in six cancer panels with LC50 values of <9 microM, and is especially effective against colon cancer, melanoma, renal cancer and breast cancer. Compound 1 selectively affects cell growth against renal cancer A 498 cell line and compound 4 affects cell growth against breast cancer MDA-MB-231/ATCC cell line with an LC50 value 0.06 microM. Increases in the chain length of the linker in 2,2'-PBD dimers significantly increase the cytotoxic potency and increases in the number of pyrrole groups in the PBD-polyamide conjugates similarly increase the cytotoxic potency.

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Anzini, M.; Cappelli, A.; Vomero, S.; Botta, M.; Cagnotto, A. 1990: 5-HT and benzodiazepine receptor ligands. III. Synthesis and receptor affinities of 1,2,4-triazolo[4',3':1,6]pyridazino[4,5-b]quinoline and 2,3-dihydro-9-phenyl-1H-pyrrolo[3,4-b]quinoline-1-one derivatives Farmaco 45(11): 1169-1179
Gronski, P.; Bauer, R.; Bodenbender, L.; Kanzy, E.J.; Schmidt, K.H.; Zilg, H.; Seiler, F.R. 1988: On the nature of IgG dimers. I. Dimers in human polyclonal IgG preparations: kinetic studies Behring Institute Mitteilungen 82: 127-143
Singh, A.K.; Lown, J.W. 2000: Design, synthesis and antitumor cytotoxicity of novel bis-benzimidazoles Anti-Cancer Drug Design 15(4): 265-275
Massa, S.; Corelli, F.; Pantaleoni, G.C.; Palumbo, G. 1983: Heterocyclic systems. IV. Synthesis and CNS activity of derivatives of 4H,6H-pyrrolo[1,2-a][4,1]-benzoxazepine Il Farmaco; Edizione Scientifica 38(11): 893-903
Ferlin, M.G.; Chiarelotto, G.; Basadonna, O.; Gia, O.; Mobilio, S.; Baccichetti, F.; Carlassare, F. 1989: 1H-pyrrolo[2,3-f]quinoline and isoquinoline derivatives: synthesis and antiproliferative activity Farmaco 44(12): 1141-1155
Fujisawa, S.; Atsumi, T.; Kadoma, Y.; Ishihara, M.; Ito, S.; Yokoe, I. 2004: Kinetic radical scavenging activity and cytotoxicity of 2-methoxy- and 2-t-butyl-substituted phenols and their dimers Anticancer Research 24(5a): 3019-3026
Vega, S.; Gil, M.S.; Darias, V.; Sanchez Mateo, C.C.; Exposito, M.A. 1995: Synthesis and pharmacological study of 5,6,8,9-tetrahydro-4H, 7H-pyrrolo[1,2-a]cyclopenta[b]thieno[3,2-f][1,4]diazepines Die Pharmazie 50(1): 27-33
Massa, S.; Corelli, F.; Artico, M.; Mai, A.; Silvestri, R.; Pantaleoni, G.C.; Palumbo, G.; Fanini, D.; Giorgi, R. 1989: 5-Aroyl-5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepin-4-carboxylic acids: synthesis and analgesic and neurobehavioral activity Farmaco 44(2): 109-123
Grandolini, G.; Ambrogi, V.; Perioli, L.; Giannaccini, G.; Lucacchini, A.; Martini, C. 1996: Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. X--Synthesis and inhibition of benzodiazepine receptor binding of new 1,4-thiazine and 1,5-thiazepine polycondensed heterocycles with steroidal structure Farmaco 51(3): 203-207
Wang, Q.W.; Zheng, Z.F.; Yang, P.S. 1994: Studies on endotoxin lipopolysaccharides of infected root canals in cytotoxicity in vitro Zhonghua Kou Qiang Yi Xue Za Zhi 29(4): 217-219
Lavrin, D.H.; Herberman, R.B.; Nunn, M.; Soares, N. 1973: In vitro cytotoxicity studies of murine sarcoma virus-induced immunity in mice Journal of the National Cancer Institute 51(5): 1497-1508
Roma, G.; Ermili, A.; Balbi, A. 1977: Studies on 1,5-benzodiazepine. I. Derivatives of 4-amino-1,5-benzodiazepine Il Farmaco; Edizione Scientifica 32(2): 81-91
Ambrogi, V.; Grandolini, G.; Perioli, L.; Giusti, L.; Lucacchini, A.; Martini, C. 1993: Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. VII. Synthesis and inhibition of benzodiazepine receptor binding of some 4,5-dihydro-tetrazolo[5,1-d]-1,5-benzothiazepines and 5-phenyl-s-triazolo[3,4-d]-1,5-benzothiazepines Farmaco 48(5): 665-676
Philpott, G.W.; Bower, R.J.; Parker, K.L.; Shearer, W.T.; Parker, C.W. 1974: Affinity cytotoxicity of tumor cells with antibody-glucose oxidase conjugates, peroxidase, and arsphenamine Cancer Research 34(9): 2159-2164
Kumar, L.; Lal, N.; Kumar, V.; Sarswat, A.; Jangir, S.; Bala, V.; Kumar, L.; Kushwaha, B.; Pandey, A.K.; Siddiqi, M.I.; Shukla, P.K.; Maikhuri, J.P.; Gupta, G.; Sharma, V.L. 2013: Azole-carbodithioate hybrids as vaginal anti-Candida contraceptive agents: design, synthesis and docking studies European Journal of Medicinal Chemistry 70: 68-77
Wang, Y.-j.; Cao, X.; Liu, X.-y.; Lu, X.-l.; Li, Y.-y.; Jiao, B.-h. 2016: Antibody-drug conjugates: design and clinical progress Yao Xue Xue Bao 51(8): 1209-1216
Sokolova, M.V.; Pomelova, V.G.; Chudinov, A.V.; Gaĭdamovich, S.I.; Leonov, S.V.; Kharitonenkov, I.G.; Bychenkova, T.A.; Busel, E.P.; Zlobin, V.N. 1991: The design and trial of conjugates for performing lanthanide immunofluorescence analysis Voprosy Virusologii 36(2): 140-142
Biagi, G.; Dell'Omodarme, G.; Ferretti, M.; Giorgi, I.; Livi, O.; Scartoni, V.; Tiscione, E. 1990: Studies on 1,2,3-triazole derivatives as in vitro inhibitors of prostaglandin synthesis Farmaco 45(11): 1181-1192
Sobczak, A.; Blazejczyk, M.; Piszczek, G.; Zhao, G.; Kuznicki, J.; Wojda, U. 2005: Calcium-binding calmyrin forms stable covalent dimers in vitro, but in vivo is found in monomeric form Acta Biochimica Polonica 52(2): 469-476
Hao, A.Jun.; Deng, Y.Jie.; Suo, X.Bin.; Cao, Y.Hong. 2006: Synthesis and characteristics of the fluorouracil-dextran conjugates Die Pharmazie 61(5): 489-490