A new class of fused quinazolines has been designed and synthesized via copper-catalyzed Ullmann type C-N coupling followed by intramolecular cross-dehydrogenative coupling reaction in moderate to good yields. The synthesized compounds were tested for in vitro antibacterial activity against three Gram negative (Escherichia coli, Pseudomonas putida, and Salmonella typhi) and two Gram positive (Bacillus subtilis, and Staphylococcus aureus) bacteria. Among all tested compounds, 8ga, 8gc, and 8gd exhibited promising minimum inhibitory concentration (MIC) values (4-8 μg/mL) for all bacterial strains tested as compared to the positive control ciprofloxacin. The synthesized compounds were also evaluated for their in vitro antifungal activity against Aspergillus niger and Candida albicans and compounds 8ga, 8gc, and 8gd having potential antibacterial activity also showed pronounced antifungal activity (MIC values 8-16 μg/mL) against both strains. The bactericidal assay by propidium iodide and live-dead bacterial cell screening using a mixture of acridine orange/ethidium bromide (AO/Et·Br) showed considerable changes in the bacterial cell membrane, which might be the cause or consequence of cell death. Moreover, the hemolytic activity for most potent compounds (8ga, 8gc, and 8gd) showed their safety profile toward human blood cells.

The present manuscript reports the synthesis of multistimulus-responsive smart supramolecular hydrogels derived by in situ coating of silver nanoparticles (Ag NPs) on colloidal cytidine-5'-monophosphate-capped β-FeOOH nanohybrids (β-FeOOH@5'-CMP) under physiological conditions forming a polycrystalline building block (Ag-coated β-FeOOH@5'-CMP). The presence of Ag in the binary nanohybrids induces the puckering of ribose sugar, bringing a change in its conformation from C2'-endo to C3'-endo, which enhanced the supramolecular interactions among different moieties of other building blocks to construct a porous network of hydrogels in the self-assembly via the formation of a micellar structure. Such a supramolecular network in hydrogel is also evidenced by the reversible sol⇌gel transformation under multistimulus-responsiveness in a narrow range of pH, temperature, and sonication, as well as by the manifestation of rapid self-healing and injectability features. As-synthesized hydrogels exhibiting shear-thinning behavior under higher strain and converting back into the sol under low strain, suggests their potential for localized drug delivery. The presence of Ag NPs in the hydrogel enhanced its viscoelastic properties, % swelling (580) and loading capabilities (590 mg g-1) for methylene blue (MB), and its controlled release over days (∼2-30) as a function of pH. It displayed excellent surface-enhanced Raman spectroscopy activity allowing to detect MB-like drug molecules at ≤10-12 M. Thus, the as-synthesized hydrogels represent a unique superparamagnetic nanosystem consisting of all greener components (5'-CMP/β-FeOOH/Ag) with superior viscoelastic, sensing, and antimicrobial properties, displaying multistimulus-responsiveness (pH/temperature/sonication), thereby suggesting their vast potential for biomedical and environmental applications.

Four lipopeptaibols, namely, lipovelutibols A-D, were recently isolated from psychrotrophic fungus Trichoderma velutinum and reported to have significant cytotoxic activity against HL-60, MDA-MD-231, A549, and LS180 cancer cell lines. In the present study, these peptides were synthesized in a solution using a segment condensation approach. The conformational analysis of these peptides carried out using CD spectrophotometry revealed the formation of 310-helix, and the NMR-VT experiments showed intramolecular hydrogen bonding for NH-5, NH-6, and NH-7. Lipovelutibol D showed potent cytotoxic activity and was chosen for lead optimization. It involved N- and C-terminal truncation, N- and C-terminal modification, random deletion, l/d configuration replacement, and other synthetic analogues. These were tested against various breast cancer cell lines. The C-terminal aldehyde analogue resulting from lead optimization of lipovelutibol D was found to have almost twofold enhanced cytotoxicity against MDA-MB-231 breast cancer cell lines.

The formation of binary nanohybrids consisting of environmentally benign components, γ-Fe2O3, chitosan (CS), and Ag (Ag-γ-Fe2O3@CS) (CSIOAg), containing very low concentration of Ag NPs (≤1.2 μM), has been reported. In the as-synthesized nanohybrids, the presence of γ-Fe2O3 (8.5 ± 0.8 nm) and Ag (5.9 ± 0.5 nm) are revealed by optical, XRD, TEM, and XPS analyses, and their presence in cubic phase is determined by XRD and SAED measurements. The catalytic activity of CSIOAg has been analyzed by performing the reduction of certain toxic dyes. Under all kinetic conditions, the reaction is attended by an induction period, which is reduced upon increasing [Ag] and [Dye] in a specific concentration range, as well as temperature, suggesting restructuring of the surface prior to reduction. In case of methyl orange (MO), the reduction results in its cleavage to produce N,N-dimethyl-1,4-phenylenediamine and sodium sulfanilate in a significantly higher (>97%) yield in a bimolecular reaction between MO and BH4 -. The duration of induction period is regularly decreased and the rate of reduction (k app) increases linearly with increasing Ag in the wide concentration range (0.03-2.4 μM). The reduction takes place with a second-order rate constant of 2.7 × 104 dm3 mol-1 s-1, which is >3.5-fold higher than that in the absence of chitosan (IOAg) under identical experimental conditions. The kinetics of reduction of MO is controlled by the nature and extent of its adsorption on the catalyst surface. The weaker binding between MO and Ag catalyst only allows its effective reduction. The XPS analysis of CSIOAg and IOAg containing the same amount of Ag (1.2 μM) showed its higher amount on the surface of CSIOAg (0.12%) as compared to that of IOAg (0.09%). Detailed kinetic analysis of MO reduction, performed under pseudo-kinetic conditions for both the nanohybrids revealed them to follow Langmuir-Hinshelwood kinetic model and exhibited the recyclability up to 10 cycles with fairly high reaction efficiency and TOF, suggesting it to be a sustainable green nanosystem.