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A novel series of 6-substituted-8-(1-cyclohexyl-1 H -benzo[ d ]imidazole-6-yl)imidazo[1,2- a ]pyrazine and 6-substituted-8-(1-benzyl-1 H -benzo[ d ]imidazole-6-yl)imidazo[1,2- a ]pyrazine is first time synthesized and screen in vitro biological activity for 60 human cancer cell lines representing nine different cancer types. Derivatives 10 and 36 show antitumor activity for all tested cell lines, display comparable full panel mean-graph midpoint growth inhibition (MG_MID GI 50) values of 2.10 and 2.23 μ M, respectively. Furthermore, these derivatives show strong binding interactions with DNA and bovine serum albumin (BSA), studied through absorption, emission, and circular dichroism techniques. These spectroscopic studies reveal that imidazo[1,2- a ]pyrazine-benzimidazoles 10 and 36 , intercalate with ct-DNA as a leading interaction for fundamental biologically significant effects, with monobenzimidazole show better activity than bisbenzimidazole. These experiments have confirmed that the imidazo[1,2- a ]pyrazine and benzimidazole moieties are efficient pharmacophores to trigger binding to DNA. These compounds have also interacted with bovine serum albumin protein that demonstrating high values of binding constant. A novel series of imidazo[1,2- a ]pyrazine-benzimidazole is first time synthesized and screen in vitro biological activity for 60 human cancer cell lines representing nine different cancer types. Image 1 • A new series of imidazo[1,2- a ]pyrazine-benzimidazole conjugates has been synthesized. • Single X-ray crystal determination of compound 9. • In vitro evaluation of synthesized compounds for their antitumor activity. • Mode of interactions was studied with ct-DNA. • Transportation of derivative was studied with bovine serum albumin. [ABSTRACT FROM AUTHOR]

Quinazolinone and benzimidazole represent as important and abundant classes of fused nitrogen-containing heterocycle. A series of two isomeric quinazolinone-benzimidazole conjugates is synthesized and substitutes with different aromatic rings. These compounds are well characterized by 1 H and 13 C NMR as well as mass spectrometry. Compounds are then evaluated by dihydrofolate reductase inhibitory activity. In vitro assay shows that some compounds are exhibiting significant dihydrofolate reductase inhibitory activities. Compound 14 shows comparable or even superior inhibitory activity with IC 50 value of 0.011 μM in contrast to methotrexate (IC 50 = 0.02 μM). The preliminary interactive investigation of compound 14 is studied with calf thymus DNA by UV–visible and fluorescence spectroscopy. It reveals that compound 14 is effectively intercalated with ct-DNA to form 14 .DNA complex which is further supported by ethidium bromide (EB) displacement studies. The compound 14 also shows strong interaction with bovine serum albumin that can helpful in the design, modification and screening of drug molecules. The binding interactions of compound 14 with bovine serum albumin demonstrate that hydrogen bonds and van der Waals forces play important roles in the strong association of compound 14 .BSA. These compounds can be considered as useful templates for future development and further derivatization or modification will be helpful to obtain more potent compounds. [ABSTRACT FROM AUTHOR]

A novel series of triazine-benzimidazole analogs has been designed and synthesized for their in vitro anticancer activities. Four compounds ( 6 , 16 , 17 and 20) were identified as highly potent anticancer agents against 60 human cancer cell lines with GI 50 in the nanomolar range. To improve the drug applications toward cancer cells, there is a need to couple these compounds to some carrier macromolecules. Following this approach, the interaction between triazine-benzimidazole analogues and bovine serum albumin (BSA) has been investigated with UV–Visible and fluorescence spectroscopic methods under physiological conditions. The observed fluorescence quenching indicates that these compounds could efficiently bind with BSA and be transported to the target site. [ABSTRACT FROM AUTHOR]

A new series of triazine–benzimidazole hybrids has been synthesized with different substitution of primary and secondary amines at one of the position of triazine in moderate to good yields. These compounds were evaluated for their inhibitory activities over 60 human tumor cell lines at one dose and five dose concentrations. Compounds 6b , 8 and 9 showed broad spectrum of antitumor activities with GI 50 values of 9.79, 2.58 and 3.81 μM, respectively. DNA binding studies also indicated strong interaction properties of these compounds. These synthesized compounds also showed inhibition of mammalian dihydrofolate reductase (DHFR). Compound 6b was depicted as the most active member of DHFR inhibitor with IC 50 value of 1.05 μM. Molecular modelling studies were used to identify the stabilized interactions of Compound 6b within the active site of enzyme for DHFR. [ABSTRACT FROM AUTHOR]

In an effort to identify novel compounds for the treatment of cancer, a diverse array of potential bioactive hybrid, purine-benzimidazole was synthesized in good yields through nucleophilic substitution at C6 position of purine ring with versatile cyclic amines at C2 position. The structures of newly prepared compounds were confirmed by IR, 1 H, 13 C NMR, mass spectroscopy and, in case of 19 , by single crystal X-ray diffraction analysis. The newly synthesized compounds were evaluated against 60 human tumour cell lines at one dose concentration level. Compound 6 exhibited significant growth inhibition and was evaluated as 60 cell panel at five dose concentration levels. Compound 6 proved to be 1.25 fold more active than the positive control 5-FU, with GI 50 value of 18.12 μM (MG-MID). Interaction of the compounds with Aurora-A enzyme involved in the process of propagation of cancer, has also been investigated. Compound 6 showed selectivity towards Aurora-A kinase inhibition with IC 50 value of 0.0l μM. Molecular docking studies in the active binding site provided theoretical support for the experimental biological data acquired. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel regioisomeric hybrids of quinazoline/benzimidazole viz. (3-allyl-2-methyl-3H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine and (1-allyl-2-methyl-1H-benzimidazol-5-yl)-(2-substituted-quinazolin-4-yl)-amine of biological interest were synthesized. All the synthesized compounds were well characterized by 1H and 13C NMR as well as mass spectroscopy. The newly synthesized compounds were screened for in vitro antitumor activities against 60 tumor cell lines panel assay. A significant inhibition for cancer cells were observed with compound 9 and also more active against known drug 5-fluorouracil (5-FU) in some tumor cell lines. Compound 9 displayed appreciable anticancer activity against leukemia, colon, melanoma, renal and breast cancer cell lines. [Copyright &y& Elsevier]

The ionic inputs to new fluorophore have been mimicked as a superimposed electronic molecular keypad lock and half-subtractor. [ABSTRACT FROM AUTHOR]

One of the approaches clinically used for the early diagnosis of cancer is based on the detection and quantification of spermine from the urine. Herein, we have developed platforms of ionic self-assemblies ENS-1 and ENS-2 which elicit highly selective fluorescence quenching with spermine. ENS-1 can detect as low as 6 nM spermine from urine and blood serum samples – a significantly lower concentration required for the early diagnosis of cancer. ENS-1 and ENS-2 could be generated in situ through ionic self-assembly of 1-(2-naphthyl)benzimidazolium based fluorescent molecules DI-NAP and TET-NAP with sodium dodecylsulfate (SDS) in HEPES buffer (containing 5% DMSO) which shows blue fluorescence centred at 425 nm. The practicability of ENS-1 for determining spermine from natural samples could be ensured by the stability of its fluorescence intensity over a period of more than a month, over a broad pH range of 5–10 and also its ability to retain fluorescence intensity at 25 °C even after variation of its temperature between 10 and 60 °C. The mechanism of interaction of ENS-1 and ENS-2 with spermine, as obtained from fluorescence, UV–vis spectroscopy and DLS studies reveals binding of the spermine on surface of ENS-1 and ENS-2 responsible for the observed changes. [ABSTRACT FROM AUTHOR]

ESIPT based benzimidazole derivative probe 1 with electron withdrawing group has been synthesized and investigated their photophysical behavior towards various anions. The probe 1 has been used for selective estimation of CN − and signaled the binding event through formation of new absorption band at 380 nm and emission band at 430 nm with CN − . The addition of various metal ions to probe 1 in aqueous system showed selectivity towards Cu 2+ and Hg 2+ ions as compared to other metal ions, and signal the binding event through formation of new absorption band at 375 nm and decrease in absorption intensity respectively. Thus, probe 1 act as chemosensor for CN − ions which restricts the ESIPT emission at 485 nm due to H-bonding interactions between O H to nitrogen of benzimidazole moiety to release its enol emission. The chemical inputs of CN − and Cu 2+ ions to probe 1 mimicked a sequence dependent operation of an exclusive-OR (XOR) logic gate. The binding behavior of probe 1 towards CN − and Cu 2+ has also been confirmed through DFT calculations. [ABSTRACT FROM AUTHOR]

Abstract: By combining the structural features of quinazoline and benzimidazole, new hybrid regioisomeric molecules with substituted primary amines have been synthesized. Evaluation of these molecules over 60 cancer cell line panel has identified three molecules as most potent anticancer agents. Compound 10 showed ten and eleven folds more activity than respective quinazoline and benzimidazole class of compounds with GI50 value of 1.64μM. Compound 11 (GI50 value of 0.81μM) showed almost twenty and twenty-two fold more activity than quinazoline and benzimidazole analogue, respectively while compound 12 (GI50 value of 4.52μM) has four fold more activity than quinazoline and benzimidazole analogue. In vitro evaluation of compound 11 exhibited remarkable anticancer activity towards colon cancer cell lines and prostate cancer cell lines at five dose concentrations with GI50 values of 0.34 and 0.31μM, respectively. [Copyright &y& Elsevier]

Abstract: A series of novel coumarin–benzimidazole hybrids, 3-(1H-benzo[d]imidazol-2-yl)-7-(substituted amino)-2H-chromen-2-one derivatives of biological interest were synthesized. Six out of the newly synthesized compounds were screened for in vitro antitumor activity against preliminary 60 tumor cell lines panel assay. A significant inhibition for cancer cells was observed with compound 8 (more than 50% inhibition) compared with other compounds and active known drug 5-fluorouracil (in some cell lines) as positive control. Compound 8 displayed appreciable anticancer activities against leukemia, colon cancer and breast cancer cell lines. [Copyright &y& Elsevier]

Excited State Intramolecular Proton Transfer based benzimidazole derivative having push–pull effect has been synthesized and investigated their photophysical behavior towards various anions. The probe 2 has been used for selective estimation of F − and CN − anions and signaled the binding event through formation of new absorption band at 465 nm. The probe 2 opens different emission channels at 425 nm in the presence of CN − ions and two new emission bands at 435 nm and 365 nm in case of F − ions. The probe 2 behaved as chemodosimeter for CN − ions which have been proved by 1 H NMR and whereas fluoride caused hydrogen bonding interactions with probe 2 and restricted the ESIPT emission at 505 nm from OH to nitrogen of benzimidazole moiety to release its enol emission. The differential behavior of F − ions and CN − have been confirmed through DFT calculations. [ABSTRACT FROM AUTHOR]