A library of piperate derivatives 3-25 was synthesized in a two-step reaction scheme starting from piperine 1, which was converted to piperic acid 2 first, and then reacted with various alkyl and aryl halides to afford the final products. Compounds were fully characterized and evaluated for their multitarget potential against well-established drug targets involved in diabetes and Alzheimer's diseases. In vitro assay revealed strong inhibitory activity against acetylcholinesterase (AChE), butylcholinesterase (BChE), α-glucosidase, and α-amylase. Compounds 6-15, 19, and 21-23 were potent inhibitors of AChE, and compounds 6-8, 12-15, 19, and 21-23 were also more effective inhibitors of BChE than the standard donepezil. Compounds bearing halogens (F, Cl, and Br) exhibited noteworthy inhibitory potency against both targets. In addition, compounds 2, 3, 17, 18, and 25 were recognized as potent α-glucosidase and α-amylase inhibitors, outperforming standard acarbose. In particular, piperic acid (2) and compounds containing the cyanomethyl (compound 3), 3-methoxyphenyl (compounds 17, 18), and 2-nitrophenyl (compound 25) moieties showed remarkable inhibitory potential. Further, kinetic studies were conducted to unravel the inhibition mechanism against all four enzymes, while in silico studies identified key interactions between inhibitors and the active-site residues of each target. All compounds also displayed reasonable antioxidant potential, as evidenced by FRAP, CUPRAC, and DPPH assays, compared with the standard butylated hydroxytoluene (BHT). Detailed pharmacokinetic and ADME profiles were also predicted to assess the druggability of the compounds. The identified ligands have multitarget potential to inhibit the key enzymes associated with diabetes and Alzheimer's. They may serve as lead candidates for later stages of drug development.

Marine sponges are sessile invertebrates found in moderate, arctic, and tropical regions, serving as a valuable reservoir of bioactive compounds, particularly Pro-rich peptides. Among these, cyclic peptides have attracted significant interest due to their diverse therapeutic properties. One notable example is Stylissatin A (SA), a Pro-rich cyclic peptide reported from the marine sponge Stylissa massa. SA and its analogues have shown promising biological activities, including anti-inflammatory, anticancer, and anti-obesity effects. Despite the vast potential of marine-derived peptides, only a small number have progressed to the pharmaceutical market. Cyclic peptides like SA offer unique opportunities for molecular modifications and total synthesis, enabling the enhancement of potency, improvement of physicochemical properties, and optimization of synthetic yields. This review highlights the synthetic strategies developed for the total synthesis of SA, explores its structural features and related analogues, and discusses their therapeutic potential, underscoring the promise of SA-based scaffolds as novel peptide-based drug candidates.

The cyclic peptide stylissatin A (STA) was obtained from the Papua New Guinean marine sponge Stylissa massa as a potent nitric oxide (NO) inhibitor. Among its reported analogs, cyclo-{Glu(6), Ala(2)}-STA 1 potently inhibited the interleukin-2 and proliferation of T-cells indicating position 2 of sequence playing important part in biological activities of this compound. In current studies, second generation analogs of STA were synthesized around its most active analog 1 by screening position 2 of analog 1 with different amino acid. All analogs 2-6 were identified by mass, and NMR techniques. The synthesized analogs were also evaluated against NO generation by lipopolysaccharide (LPS)-stimulated murine J774.2 macrophages, ROS inhibition from whole blood phagocytes, and T-cell proliferation from Jurkat cells. All analogs were found to be inactive towards interleukin-2, T-cells proliferation, and ROS inhibition. The analog 2 showed a potent suppression of NO (IC50 = 46.0 +/- 2.2 mu M) that was superior to the activity reported for natural product STA. Further attempts to optimize analog 2 afforded new nitric oxide inhibitors 2a-2f which were found less active than 2. The analog 2 also downregulated the transcription of pro-inflammatory molecules, tumor necrosis factor-alpha, interlukin-1 beta, caspase-1 and ASC which further highlights its anti-inflammatory and possible therapeutic potential. Analog 2 was non-toxic to BJ and Vero cell lines of normal mammalian origin.

As the technologies for peptide synthesis and development continue to mature, antimicrobial peptides (AMPs) are being widely studied as significant contributors in medicinal chemistry research. Furthermore, the advancement in the synthesis of dendrimers’ design makes dendrimers wonderful nanostructures with distinguishing properties. This study foregrounds a temporin SHa analog, [G10a]-SHa, and its dendrimers as globular macromolecules possessing anticancer and antibacterial activities. These architectures of temporin SHa, named as [G10a]-SHa, its dendrimeric analogs [G10a]2-SHa and [G10a]3-SHa, and [G10a]2-SHa conjugated with a polymer molecule, i.e., Jeff-[G10a]2-SHa, were synthesized, purified on RP-HPLC and UPLC and fully characterized by mass, NMR spectroscopic techniques, circular dichroism, ultraviolet, infrared, dynamic light scattering, and atomic force microscopic studies. In pH- and temperature-dependent studies, all of the peptide dendrimers were found to be stable in the temperature range up to 40–60 °C and pH values in the range of 6–12. Biological-activity studies showed these peptide dendrimers possessed improved antibacterial activity against different strains of both Gram-positive and Gram-negative strains. Together, these dendrimers also possessed potent selective antiproliferative activity against human cancer cells originating from different organs (breast, lung, prostate, pancreas, and liver). The high hemolytic activity of [G10a]2-SHa and [G10a]3-SHa dendrimers, however, limits their use for topical treatment, such as in the case of skin infection. On the contrary, the antibacterial and anticancer activities of Jeff-[G10a]2-SHa, associated with its low hemolytic action, make it potentially suitable for systemic treatment.

Recently, researchers are focusing on the synthesis of Schiff base complexes due to their promising biological activities and frequent use in the pharmaceuticals. In the present study we synthesized Schiff base of salicyldehyde and 2, 4-dinitrophenylhydrazine by modified method and its novel metal complexes with Cu (II), Zn (II), Co (II), Ni (II), Mn (II), V (II) and AU (IIII). For spectroscopic studies and characterization, UV-Vis and FT-IR spectroscopy were used. The Schiff base and its metals complexes were tested for antimicrobial, cytotoxic and antioxidant activities. Significant results are showed by the all synthesized complexes.

Environmental pollution due to heavy metal ions is a serious health concern worldwide. In this study we have developed a new conjugate of cyclic peptide stylissatin A analogue with silver nanoparticle. The nanoparticles conjugated peptide was found highly selective sensor for Hg2+ in tap water and human blood. Cyclic peptide conjugate of silver nanoparticles (CP-AgNPs) were synthesized using chemical reduction method and characterized using UV-visible, FTIR, Zetasizer and atomic force microscopic techniques (AFM). CP-AgNPs were found to be highly stable in a wide range of pH and electrolyte concentration up to 1 M NaCl. The nanoparticles were spherical in shape and average sizes were found to be in the range of 60 to 80 nm. The photophysical potential of CP-AgNPs towards metal ions was examined using UV-visible spectroscopy. CP-AgNPs were found to be highly selective for Hg2+ ions as no interference was observed in the competitive experiments. The change in the absorption intensity of CP-AgNPs was directly proportional to the concentration of Hg+2 over a wide range of concentration (1-100 mu M). Jobs plot experiment showed 1:2 binding stoichiometry between CP-AgNPs and Hg2+. Moreover CP-AgNPs were effectively used for the detection of Hg2+ in the laboratory tap water and blood plasma. (C) 2019 Elsevier B.V. All rights reserved.

Objective: To determine the frequency of biochemical abnormalities in developmentally normal children presenting with new onset seizures Methodology: This descriptive cross sectional study was carried out in 131 children presenting in Pediatrics emergency department, Liaquat National Hospital from March 1, to September 30, 2015. Children with very first episode of seizure, aged >lmonth to less than or equal to 12 years with either active seizures or with history of seizure, as witnessed by the care taker were included in the study. Serum glucose, calcium and magnesium were analyzed and frequency of biochemical abnormalities was determined. Results: Abnormal serum glucose was observed in 4.5% children and abnormal calcium and magnesium were seen in 18.3% and 2.2% cases, respectively. An overall biochemical abnormality (serum glucose, calcium and magnesium) in children with new onset seizures was observed in 27 (20.6%) children. Both serum glucose and calcium were abnormal in 3(2.2%) cases and both serum calcium and magnesium were abnormal in 3(2.2%) cases. Conclusion: The diagnosis of biochemical abnormalities is imperative because it alters the therapeutic management of these patients. These tests could be particularly beneficial in children under 1 year, since signs of serum chemistry disturbances are non-specific or are even absent at this age. In older children, these tests should be judiciously advised as guided by history and examination.