Xylanase immobilization on magnetite and magnetite core/shell nanocomposites using two different flexible alkyl length organophosphonates: Linker length and shell effect on enzyme catalytic activity.

Magnetite and magnetite core/shell (Fe3O4/SiO2) nanoparticles were synthesized and functionalized with two different alkyl chain length linkers that were 3-Phosphonopropionic acid (3-PPA) and 16-Phosphonohexadecanoic acid (16-PHDA). Xylanase (EC 3.2.1.8, endo-1,4-xylanase, endo-1), was immobilized on as synthesized bare and silica coated magnetite nanoparticles via well-known EDC coupling. Transmission Electron Microscopy (TEM), Field Emission Scanning Electron Microscopy (FESEM), X-Ray Diffraction Spectroscopy (XRD), X-ray Photoelectron Spectroscopy (XPS), Dynamic Light Scattering (DLS) and Thermogravimetric analysis (TGA) techniques were utilized to characterize all the modifications. The flexible linker chain length plays a vital role in the catalytic attributes of the immobilized enzyme. Result shows that long chain alkyl linker grafted magnetite and magnetite core/silica shell nanoparticles exhibited a superior performance in terms of lower Km, higher catalytic efficiency and better reusability. Furthermore, the immobilized xylanase shows improved tolerability performance at a wide range of pH and temperature. Silica-coated magnetite nanoparticles bound xylanase through 16-PHDA retained 90% of its initial activity after 10 consecutive cycles, further emphasize on the beneficial effect of linker chain length and inert silica coating.

Quinazolinone-benzimidazole conjugates: Synthesis, characterization, dihydrofolate reductase inhibition, DNA and protein binding properties.

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 1H and 13C 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 IC50 value of 0.011µM in contrast to methotrexate (IC50=0.02µM). 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.

Novel pyrazolo[3,4-d]pyrimidine with 4-(1H-benzimidazol-2-yl)-phenylamine as broad spectrum anticancer agents: Synthesis, cell based assay, topoisomerase inhibition, DNA intercalation and bovine serum albumin studies.

A series of new pyrazolo[3,4-d]pyrimidine possessing 4-(1H-benzimidazol-2-yl)-phenylamine moiety at C4 position and primary as well as secondary amines at C6 position has been designed and synthesized. Their antitumor activities were evaluated against a panel of 60 human cancer cell lines at National Cancer Institute (NCI). Six compounds displayed potent and broad spectrum anticancer activities at 10 µM. Compounds 8, 12, 14 and 17 proved to be the most active and efficacious candidate in this series, with mean GI50 values of 1.30 µM, 1.43 µM, 2.38 µM and 2.18 µM, respectively against several cancer cell lines. Further biological evaluation of these compounds suggested that these compounds induce apoptosis and inhibit human topoisomerase (Topo) IIα as a possible intracellular target. UV-visible and fluorescence studies of these compounds revealed strong interaction with ct-DNA and bovine serum albumin (BSA).

Synthesis and in vitro evaluation of novel triazine analogues as anticancer agents and their interaction studies with bovine serum albumin.

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 GI50 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.

Synthesis, in vitro antitumor activity, dihydrofolate reductase inhibition, DNA intercalation and structure-activity relationship studies of 1,3,5-triazine analogues.

A series of triazine-benzimidazoles with 4-fluoroaniline substitution has been designed and synthesized. These compounds were further substituted with different primary and secondary amines. The structures of newly synthesized compounds were confirmed by (1)H, (13)C NMR, mass spectrometry and, in case of compound 18, by single crystal X-ray diffraction analysis. The newly synthesized compounds were evaluated against 60 human tumor cell lines at one dose and five dose concentration levels. Compounds 7, 8 and 22 have been found to be the most active antitumor agents with GI50 values of 1.77, 1.94 and 2.87µM, respectively. The synthesized compounds were then evaluated for their inhibitory activity to mammalian dihydrofolate reductase. Compound 22 was depicted as the most active compound for the inhibition of dihydrofolate reductase with IC50 value of 2.0nM. DNA binding studies were also revealed strong interacting properties of triazine derivatives towards calf thymus-DNA.

Triazine as a promising scaffold for its versatile biological behavior.

Among all heterocycles, the triazine scaffold occupies a prominent position, possessing a broad range of biological activities. Triazine is found in many potent biologically active molecules with promising biological potential like anti-inflammatory, anti-mycobacterial, anti-viral, anti-cancer etc. which makes it an attractive scaffold for the design and development of new drugs. The wide spectrum of biological activity of this moiety has attracted attention in the field of medicinal chemistry. Due to these biological activities, their structure-activity relationship has generated interest among medicinal chemists and this has culminated in the discovery of several lead molecules. The outstanding development of triazine derivatives in diverse diseases within very short span of time proves its magnitude for medicinal chemistry research. Therefore, these compounds have been synthesized as target structure by many researchers, and were further evaluated for their biological activities. In this review, we have compiled and discussed the biological potential of s-triazine derivatives, which could provide a low-height flying bird's eye view of the triazine derived compounds to a medicinal chemist, for a comprehensive and target oriented information for the development of clinically viable drugs.

Triazine-benzimidazole hybrids: anticancer activity, DNA interaction and dihydrofolate reductase inhibitors.

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 GI50 values of 9.79, 2.58 and 3.81µM, 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 IC50 value of 1.05µM. Molecular modelling studies were used to identify the stabilized interactions of Compound 6b within the active site of enzyme for DHFR.