Indolyl-4H-Chromene Derivatives as Antibacterial Agents: Synthesis, in Vitro and in Silico Studies.

In this study, indolyl-4H-chromene derivatives are designed and synthesised using an eco-friendly multicomponent one-pot synthesis using benzaldehydes, nitroketene N, S-acetals, and indoles combine with InCl3 , a Lewis acid catalyst, and ethanol, an environmentally acceptable solvent. Due to antibiotic resistance, assessed these Indolyl-4H-chromene derivatives for their in vitro antibacterial activity against Gram-positive and Gram-negative bacteria, including Streptococcus pyogenes, Staphylococcus aureus, Clostridium pyrogenes, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa, using the agar well diffusion method and Minimum Inhibition Concentration (MIC) assay. Three compounds, 4-(1H-indol-3-yl)-6-methoxy-N-methyl-3-nitro-4H-chromen-2-amine, 4-(1H-indol-3-yl)-3-nitro-N-phenyl-4H-chromen-2-amine and 4-(6-Fluoro-1H-Indol-3-yl)-N-methyl-3-nitro-4H-chromen-2-amine showed better zone of inhibition (mm) and Minimum Inhibition Concentration (MIC) values of 10 µg/mL to 25 µg/mL against all bacterial types. The Ki values of 278.60 nM and 2.21 nM for compound 4-(1H-indol-3-yl)-3-nitro-N-phenyl-4H-chromen-2-amine showed improved interactions with DNA gyrase B and topoIV ParE's ATP binding sites in in silico studies.

Iodine catalyzed synthesis of imidazo[1,2-a]pyrazine and imidazo[1,2-a]pyridine derivatives and their anticancer activity.

An efficient iodine-catalyzed method for synthesizing imidazo[1,2-a]pyrazines and imidazo[1,2-a]pyridines via one-pot three-component condensations has been reported. The product, generated in situ by the reaction between an aryl aldehyde and 2-aminopyridine or 2-aminopyrazine, undergoes [4 + 1] cycloaddition with tert-butyl isocyanide, affording the corresponding imidazopyrazine and imidazopyridine derivatives in good yields. The photophysical properties of these new fluorescent derivatives are also presented. The anti-cancer activities of the synthesized compounds (10a-m) and (12a-l) were evaluated against four cancer cells (Hep-2, HepG2, MCF-7, A375) and the normal Vero cell. Significant anti-cancer activities were observed and compared with the standard drug Doxorubicin. In vitro experimental results revealed that compound 12b is a promising lead with IC50 values of 11 µM, 13 µM, 11 µM, 11 µM, and 91 µM against Hep-2, HepG2, MCF-7, A375, and Vero, respectively.

Design, synthesis, and characterization of non-hemolytic antimicrobial peptides related to human cathelicidin LL-37.

We designed and synthesised the N-terminally labeled cationic and hydrophobic peptides, i.e., FFKKSKEKIGKEFKKIVQKI (P1) and FRRSRERIGREFRRIVQRI (P2) related to the human cathelicidin LL-37 peptide. The integrity and molecular weight of the peptides were confirmed by mass spectrometry. The purity and homogeneity of peptides P1 and P2 were determined by comparing LCMS or analytical HPLC chromatograms. The circular dichroism spectroscopy reveals the conformational transitions upon interaction with membranes. Predictably, peptides P1 and P2 showed a random coil structure in the buffer and formed α-helix secondary structure in TFE and SDS micelles. This assessment was further confirmed by 2D NMR spectroscopic methods. The analytical HPLC binding assay measurements revealed that peptides P1 and P2 display preferential interactions with the anionic lipid bilayer (POPC:POPG) moderately than zwitterionic (POPC). The efficacies of the peptides were tested against Gram-positive and Gram-negative bacteria. It is imperative to note here that the arginine-rich P2 exerted higher activity against all the test organisms as compared with that shown by the lysine-rich peptide P1. To test the toxicity of these peptides, a hemolytic assay was performed. P1 and P2 showed very little to no toxicity for a hemolytic assay, which is significant for P1 and P2 to be used as potential therapeutic agents in practical applications. Both peptides P1 and P2 were non-hemolytic and appeared to be more promising as they demonstrated wide-spectrum antimicrobial activity.

Design and synthesis of novel N-terminal peptides of integrin and aminopeptidase are new finding for anticancer activity.

The short peptides, containing the amino acid sequence asparagine-glycine-arginine (NGR) and arginine-glycine-aspartic acid (RGD), possess the strong binding ability to N (APN/CD13) aminopeptidase receptor and integrin proteins involved in antitumor properties are overexpressed. A novel short N-terminal modified hexapeptides P1 and P2 was designed and synthesized using the Fmoc-chemistry solid phase peptide synthesis protocol. Notably, the cytotoxicity of the MTT assay demonstrated the viability of normal and cancer cells up to lower peptide concentrations. Interestingly, both peptides show good anticancer activities against the four cancer cells and normal cells namely, Hep-2, HepG2, MCF-7, A375, and Vero and compared with standard drugs, doxorubicin and paclitaxel. Additionally, in silico studies were applied to predict the binding sites and binding orientation of the peptides for potential anticancer targets. Steady-state fluorescence measurements showed that peptide P1 exhibits preferential interactions with POPC/POPG anionic bilayers rather than the zwitterionic POPC lipid bilayers and peptide P2, did not show any preferential interaction with lipids bilayers. But impressively, peptide P2 shows anticancer activity due to the NGR/RGD motif. Circular dichroism studies demonstrated that the peptide's secondary structure changes only minimally upon binding to the anionic lipid bilayers.

Dual active 1, 4-dihydropyridine derivatives: Design, green synthesis and in vitro anti-cancer and anti-oxidant studies.

The present work describes the design of 1,4-dihydropyridines (1,4-DHPs) with diverse variations in structural and functional groups. The physico-chemical properties and drug-like molecule nature evaluations were carried out using SWISSADME. A simple, economical, eco-friendly, water-mediated and Para-Toluene sulfonic acid catalysed multicomponent and one-pot synthetic method from nitroketene N, S- acetals (NMSM) and corresponding aldehydes has been developed. All compounds (6a-u and 13a-h) were subjected to in vitro assays against two important human cancer cell lines Viz. are Laryngeal carcinoma (Hep2) and Lung adenocarcinoma (A549) cells. The reduction level of DPPH (%) used to evaluate the anti-oxidant properties. The 1,4-DHP derivatives, 6o, 6u and 6l displayed the potent anti-cancer activity with IC50 value of 10 µM, 14 µM and 10 µM against the Hep2 and 8 µM, 9 µM and 50 µM against the A549 cells. Similarly, the anti-oxidant properties of 6o, 6l and 6u at a standard concentration of 50 µg, are found to be 70.12%, 63.90% and 59.57% respectively favours the 1,4-DHP derivatives dual activity potentials. The compounds, 6o and 6l found to be equivalent with standard drug, Doxorubicin.