5444
A. Husain et al. / Bioorg. Med. Chem. Lett. 22 (2012) 5438–5444
or minimum concentration tested.31,32 The logs molar concentra-
tion also calculated of individual GI50, TGI and LC50 and repre-
sented as log10GI50, log10TGI and log10LC50, respectively. The
lowest values of response parameter were obtained with the most
sensitive cell lines.
References and notes
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On the basis of structure activity relationships, it could be con-
cluded that benzimidazole bearing oxadiazole ring were found to
have better anticancer activity than those of benzimidazole bear-
ing triazolo-thiadiazole nucleus. The anticancer activity was influ-
enced by the presence of electron withdrawing group like bromo
on ortho, meta or para position of aromatic ring. As obtained result,
the compound (4j) substituted by bromo group on ortho position
(2,6-dibromo) of phenyl ring, chemically as 3-(5-(4-amino-2,6-dib-
romophenyl)-1,3,4-oxadiazol-2-yl)-1-(1H-benzo[d]imidazol-2-
yl)propan-1-one increases the sensitivity of cell line (70.36%) and
similarly group substituted on ortho position (2,6-dibromo)of com-
pound (7d),chemically as3-(6-(4-amino-2,6-dibromophenyl)-
[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)-1-(1H-benzo[d] imid
azol-2-yl)propan-1-one decrease the sensitivity of cell line
(95.24%). On the other hand the electron releasing group like hy-
droxyl group attached with phenyl ring decrease the sensitivity
(96.71%) and (97.16%) as exhibited by compound (7c), 1-(1H-
benzo[d]imidazol-2-yl)-3-(6-(3,4,5-trihydroxyphenyl)-[1,2,4]triaz-
olo[3,4-b][1,3,4]thiadiazol-3-yl)propan-1-one
and
compound
(4i),1-(1H-benzo[d]imidazol-2-yl)-3-(5-(3,4,5-trihydroxyphenyl)-
1,3,4-oxadiazol-2-yl)propan-1-one, respectively. Finally, unsubsti-
tution phenyl rings observed in compounds 4l and 7e showed
the sensitivity of cell line (87.22%) and (85.93%), respectively.
Two series of benzimidazole bearing [1,3,4]oxadiazole and
[1,2,4]triazolo[3,4-b] [1,3,4] thiadiazole moieties comprising of 20
new compounds were successfully synthesized and among them
14 compounds were selected and evaluated for their in vitro anti-
cancer screening at the NCI, USA. Compounds showed good to
remarkable and broad-spectrum anticancer activity. The com-
pound (4j), namely 3-(5-(4-amino-2,6-dibromophenyl)-1,3,4-oxa-
diazol-2-yl)-1-(1H-benzo[d]imidazol-2-yl)propan-1-one emerged
as lead compound with broad spectrum of anticancer activities
on tumor cell lines (MG-MID 12.62 of GI50 and ꢀ5.13, ꢀ4.23,
ꢀ4.02 value of Log10GI50, Log10TGI, Log10LC50, respectively). Based
on these observations, it could be subject of further investigations
for searching potential antitumor agents. Finally it’s conceivable
that further derivatization of such compounds can be serve as no-
vel templates for anticancer chemotherapy and could be possibly
lead to more active molecules in the field of cancer chemotherapy.
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We are thankful to Dr. Thelma Dizon (Project Manager), Devel-
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(NCI), Chemotherapeutic Agents Repository, Fisher Bio Services,
Rockville, MD, USA, for in vitro anticancer screening of the com-
pounds. Thanks are also to UGC, New Delhi, Government of India,
for financial assistance in the form of Major Research Project [file
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Supplementary data
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