Synthesis of 1,2,3-triazole-piperazin-benzo[b][1,4]thiazine 1,1-dioxides: antibacterial, hemolytic and in silico TLR4 protein inhibitory activities.

In this study, we designed and synthesized a number of novel 1,2,3-triazole-piperazin-benzo[b][1,4]thiazine 1,1-dioxide derivatives and investigated their in vitro antibacterial and hemolytic activity. When compared to the lead chemical, dicloxacillin, the majority of the compounds demonstrated acceptable activity. Among them, the most promising compounds 6e, 6g, 6i, 8d, and 8e exhibited excellent antibacterial activity against the methicillin-susceptible S. aureus (MSSA), methicillin-resistant S. aureus (MRSA), and vancomycin-resistant S. aureus (VRSA) with MIC values of 1.56 ± 0.22 to 12.5 ± 1.75 µg mL-1, respectively, The percentage of hemolysis ranged from 21.3 µg mL-1 to 33.8 µg mL-1. Out of the six compounds (6i, 6e, 6f, 6g, 8e, 8d) tested compound 8e and 8d displayed minimal or negligible hemolytic activity across all the tested concentrations 29.6% and 30.2% recorded at 100 µg mL-1 concentration respectively. In silico docking studies were performed to evaluate the molecular interactions of 6e, 6f, 6g, 6i, 8d, and 8e compounds with Human, Mouse and Bovine TLR4 proteins (PDB: 3FXI, 3VQ1, 3RG1) and observed that three of the compounds (6i, 8d, and 8i) had appreciable binding energies ranging from -8.5 to -9.0 Kcal mol-1. Finally, the in silico pharmacokinetic profile was predicted for potent compounds 8d, 8e and 6i using SWISS/ADME, All compounds investigated in this study adhered to Lipinski's rule of five with slight deviation in molecular weight (8d and 8e).

Fused benzo[1,3]thiazine-1,2,3-triazole hybrids: Microwave-assisted one-pot synthesis, in vitro antibacterial, antibiofilm, and in silico ADME studies.

In this paper, we report an efficient one-pot three-component reaction sequences comprising Cu(I)-catalyzed 1,3-dipolar cycloaddition (CuAAC) followed by Cu-catalyzed arylation of resulting 1,2,3-triazole in the presence of ionic liquid [Emim]BF4 under microwave conditions involving. The newly synthesized derivatives were screened for in vitro antibacterial inhibition potency against both gram +ve and gram -ve strains. Among the tested compounds, 4f exhibited significant inhibition activity with MIC value 3.12 µg/mL against B. subtilis and S. epidermidis which is two-fold higher than the standard ciprofloxacin (6.25 µg/mL) and also displayed equipotent activity to that of the positive control against S. aureus with MIC value 6.25 µg/mL. Conjugates of the series viz. 3f and 4b against S. aureus, and 4e against E. coli have also displayed promising results with MIC values 6.25 µg/mL which is comparable to the ciprofloxacin. Also we report the anti-biofilm profiles for the potent compounds and it was observed from the results that the active derivatives 4b and 4f were not only potent antibacterial agents but also efficient inhibitors of B. subtilis and S. aureus biofilm growth. Furthermore, in silico-ADME and pharmacokinetic profiles demonstrated the druggability of the hybrids.

Novel substituted hydrazono indolo[2,1-b]quinazoline-6,12-dione analogues as cytostatic agents: Synthesis, crystal structure, biological evaluation and molecular docking studies.

A series of novel substituted hydrazono indolo[2,1-b]quinazoline-6,12-dione analogues have been synthesized and screened for their in vitro cytotoxic and antimicrobial activities. Among all the target compounds, 3c exhibited the most potent inhibitory activity against three cancer cell lines MCF-7, A549, HeLa with IC50 values 07.14±1.285µM, 09.18±0.968µM and 10.57±0.581µM respectively, while maintaining low toxicity towards non-cancer originated cell line, HEK-293. The detailed studies about molecular interactions with probable target protein indoleamine 2,3-dioxygenase (IDO1) were done by using docking simulations. The results from docking models are in consistent with the experimental in vitro cytotoxic activity conclusions i.e. 3c shows the highest binding energy -11.25kcal/mol. Furthermore, antimicrobial studies revealed that the compound 3e has shown excellent anti bacterial activity against four tested strains and the compounds 3b, 3e and 3f have shown good anti fungal activity against two tested organisms as compared with their standard drugs.

Indole-2-carboxylic acid derived mono and bis 1,4-disubstituted 1,2,3-triazoles: Synthesis, characterization and evaluation of anticancer, antibacterial, and DNA-cleavage activities.

A series of new indole-2-carboxylic acid derived mono and bis 1,4-disubstituted 1,2,3 triazoles (I(1)-I(6) and I(7)-I(12)) were synthesized and screened for their anticancer (in vitro and in vivo), antibacterial, and DNA cleavage activities. All the synthesized compounds were characterized by spectral studies. The in vitro anticancer screening results revealed that compound I(12) has registered potential activity against MCF-7, HeLa and HEK293 as compared with the standard reference drug Cisplatin. Remaining compounds have exhibited moderate to good activity against three cancer cell lines. The antibacterial activity screening results revealed that compounds, I(6) and I(12) have registered excellent inhibition against Escherichia coli and Bacillus subtilis in comparison with the standard drug Streptomycin. Compounds I(2) and I(11) have partially cleaved the DNA at 100 µg mL(-1) concentration.