Design, Synthesis, and Biological Evaluation of Novel Multifunctional Rolipram-Tranilast Hybrids As Potential Treatment for Traumatic Brain Injury.

Traumatic brain injury (TBI) is a prevalent public healthcare concern frequently instigated by mechanical shock, traffic, or violence incidents, leading to permanent nerve damage, and there is no ideal treatment for it yet. In this study, a series of Rolipram-Tranilast hybrids were designed and synthesized. The neuroprotective activities of the Rolipram-Tranilast hybrids were evaluated both in vitro and in vivo. Compound 5 has been identified as the strongest neuroprotective molecule among the series with robust anti-oxidant and anti-inflammatory potentials. Compound 5 significantly increased the heme oxygenase-1 (HO-1) levels and the phosphorylated cAMP response elements binding protein (p-CREB) while it down-regulated phosphodiesterase-4 B (PDE4B) expression in vitro. Furthermore, compound 5 remarkably attenuated TBI and had a good safety profile in mice. Taken together, our findings suggested that compound 5 could serve as a novel promising lead compound in the treatment of TBI and other central nervous system (CNS) diseases associated with PDE4B and oxidative stress.

Molecular interaction of novel benzothiazolyl triazolium analogues with calf thymus DNA and HSA-their biological investigation as potent antimicrobial agents.

The binding behaviour between calf thymus DNA and synthesized benzothiazolyl triazolium derivatives as potent antimicrobial agents was explored by means of spectroscopic applications together with molecular docking study at the sub-domain IIA, binding site I of human serum albumin (HSA). Most of the synthesized derivatives presented significant antimicrobial inhibition when compared with the clinical Norfloxacin, Chloromycin, and Fluconazole. In particular, compound 5q presented efficient anti-Bacillus subtilis, anti-Escherichia coli, anti-Salmonella typhi, and anti-Psuedomonas aeruginosa activity with low MIC values of 2-8 µg/mL which were relatively superior to the reference drugs. The preliminarily investigation of interaction studies with calf thymus DNA demonstrated that the most active compound 5q could effectively intercalate into DNA to form 5q-DNA complex. Further investigations revealed that human serum albumin could effectively transport compound 5q while molecular modelling studies with good docking score showed that hydrophobic interactions as well as hydrogen bonds played a significant role in the interaction of compound 5q with HSA. In addition, the cytotoxic investigation carried out on four different cancerous cell lines (3 human cell lines and 1 murine cell lines) by MTT assay presented that compound 5n is active against MDA cell lines with IC50 values less than 100 µg/mL.

1,3-Di-n-butylimidazolium tribromide [BBim]Br3: An efficient recyclable catalyst mediated synthesis of N-substituted azepines and their biological evaluation-interaction study with human serum albumin.

A majority of previously reported methods suffer from insufficient yields as well as more complicated experimental procedures, a smaller amount of isolated yields involving time-consuming and tiresome work-up with the use of metal catalyst and restricted scope of substrates. To overcome these issues, an environmentally benign, ionic liquid endorsed multi-component protocol to N-substituted azepines has been exploited by means of coupling aromatic amines, dimethyl/diethyl acetylene dicarboxylate, 2,5-dimethoxytetrahydrofuran using 1,3-Di-n-butylimidazolium tribromide [BBim]Br3. The catalyst can be recycled and reused for subsequent reactions. The reactivated ionic liquid could be further reused twice as an accelerator All the synthesized compounds were further screened for their antimicrobial properties against three gram positive, four gram negative, and five fungal strains with chloromycin, norflaxacin, and fluconazole as reference drugs. Most of the tested compounds presented significant potency, especially, compound 4e displayed significant antibacterial activity (MIC=1-16µg/mL) whereas compound 4k showed momentous antifungal efficacy (MIC=2-32µg/mL). In addition binding behavior of compound 4e was investigated by binding study between calf thymus DNA and compound 4e by UV-Visible absorption spectroscopy and further research about HSA interactions were carried out. The observed wavelength showed a constancy thus revealing the occurrence of non-covalent π-π stacking interactions of compound 4e and HSA.

Green synthesis, biological and spectroscopic study on the interaction of multi-component Mannich bases of imidazo[2,1-b]benzothiazoles with human serum albumin.

A series of Mannich bases of imidazo[2, l-b]benzothiazoles were prepared through one-pot multi-component reaction in the presence of water as an eco-friendly solvent. All the synthesized compounds were confirmed from IR, 1HNMR, 13CNMR, and Mass spectroscopy. Evaluation of in vitro anti-inflammatory and anti-microbial activities of all the synthesized derivatives was further accomplished. These results clearly displayed that compound 6d exhibited outstanding anti-inflammatory activity with a percentage inhibition of 70.23% by membrane stabilization method whereas 67.54% at 100µgmL-1 by the albumin denaturation method, which is comparable to the standard Diclofenac. Further screening against five fungal species (C. albicans ATCC 76615, C. mycoderma, C. utilis, A. flavus, and B. yeast) along with four gram positive (Methicillin-resistant S. aureus N315 (MRSA), Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 21216, and Micrococcus luteus ATCC 4698), and six Gram-negative bacterial strains (Escherichia coli DH52, Escherichia coli JM109, Salmonella dysenteriae, Pseudomonas aeruginosa ATCC 27853, Bacillus proteus ATCC13315 and Bacillus typhi) was carried out. These findings manifested that compound 7c displayed excellent antifungal efficacy while compound 7b revealed significant anti-microbial activity. In addition binding behaviour of compound 7b was investigated by binding study between calf thymus DNA and compound 7b by UV-Vis absorption spectroscopy and further research about HSA interactions was carried out.