Introduction: As the development of new antimicrobial agents faces a historical decline, the issue of bacterial drug resistance has become a serious dilemma that threatens the human population worldwide. Antimicrobial peptides (AMPs) represent an attractive and a promising class of antimicrobial agents. Aim: The hybridization of AMPs aimed at merging two individual active fragments of native peptides to generate a new AMP with altered physicochemical properties that translate into an enhanced safety profile. Materials and methods: In this study, we have rationally designed a new hybrid peptide via combining two individual α-helical fragments of both BMAP-27 and OP-145. The resultant peptide, was evaluated for its antimicrobial and antibiofilm activity against a range of microbial strains. The resultant peptide was also evaluated for its toxicity against mammalian cells using hemolytic and anti proliferative assays. Results: The antimicrobial activity of H4 revealed that the peptide is displaying a broad spectrum of activity against both Gram-positive and Gram-negative bacteria including standard and multidrug-resistant bacterial strains in the range of 2.5–25 μM. The new hybrid peptide displayed potent activity in eradicating biofilm-forming cells, and the reported minimum biofilm eradication concentrations were equal to the minimum inhibitory concentration values reported for planktonic cells. Additionally, H4 exhibited reduced toxicity profiles against eukaryotic cells. Combining H4 peptide with conventional antibiotics has led to a dramatic enhancement of the antimicrobial activity of both agents with synergistic or additive outcomes. Conclusion: Overall, this study indicates the success of both the hybridization and synergism strategy in developing AMPs as potential antimicrobial therapeutics with reduced toxicity profiles that could be efficiently employed to eradicate resistant bacterial strains and enhance the selectivity and toxicity profiles of native AMPs.

The recent upsurge of multidrug resistant bacteria (MDRB) among global communities has become one of the most serious challenges facing health professionals and the human population worldwide. Cationic ultrashort antimicrobial peptides (USAMPs) are a promising group of molecules that meet the required criteria of novel antimicrobial drug development. UP-5, a novel penta-peptide, displayed significant antimicrobial activities against various standard and clinical isolates of MDRB. UP-5 displayed MICs values within the range of (10–15 μM) and (55–65 μM) against Gram-positive and Gram-negative bacteria, respectively. Furthermore, UP-5 displayed antibiofilm activity with minimum biofilm eradication concentration (MBEC) value as equal to twofold higher than MIC value. At the same inhibitory concentrations, UP-5 exhibited very low or negligible toxicity toward human erythrocytes and mammalian cells. Combining UP-5 with conventional antibiotics led to a synergistic or additive mode of action that resulted in the reduction of the MIC values for some of the antibiotics by 99.7% along a significant drop in MIC values of the peptide. The stability profile of UP-5 was evaluated in full mouse plasma and serum with results indicating a more stable pattern in plasma. The present study indicates that USAMPs are promising antimicrobial agents that can avoid the negative characteristics of conventional antimicrobial peptides. Additionally, USAMPs exhibit good to moderate activity against MDRB, negligible toxicity, and synergistic outcomes in combination with conventional antimicrobial agents.

The present study aimed to synthesize thiophene carboxamide derivatives, which are considered biomimetics of the anticancer medication Combretastatin A-4 (CA-4), and compare the similarity in the polar surface area (PSA) between the novel series and CA-4. Our results showed that the PSA of the most synthesized structures was biomimetic to CA-4, and similar chemical and biological properties were observed against Hep3B cancer cell line. Among the synthesized series 2b and 2e compounds were the most active molecules on Hep3B (IC₅₀ = 5.46 and 12.58 µM, respectively). The 3D results revealed that both 2b and 2e structures confuse the surface of Hep3B cancer cell lines’ spheroid formation and force these cells to aggregate into a globular-shaped spheroid. The 2b and 2e showed a comparable interaction pattern to that observed for CA-4 and colchicine within the tubulin-colchicine-binding pocket. The thiophene ring, due to holding a high aromaticity character, participated critically in that observed interaction profile and showed additional advanced interactions over CA-4. The 2b and 2e tubulin complexes showed optimal dynamics trajectories within a time scale of 100 ns at 300 K temperature, which asserts their high stability and compactness. Together, these findings revealed the biomimetic role of 2b and 2e compounds in CA-4 in preventing cancer progression.

Thiazolidinedione (TZD), a class of drugs that are mainly used to control type 2 diabetes mellitus (T2DM), acts fundamentally as a ligand of peroxisome proliferator-activated receptors (PPARs). Besides activating pathways responsible for glycemic control by enhancing insulin sensitivity and lipid homeostasis, activating PPARs leads to exciting other pathways related to bone formation, inflammation, and cell proliferation. Unfortunately, this diverse effect of activating several pathways may show in some studies adverse health outcomes as osteological, hepatic, cardiovascular, and carcinogenic effects. Thus, a silver demand is present to find and develop new active and potent antiglycemic drugs for treating T2DM. To achieve this goal, the structure of TZD for research is considered a leading structure domain. This review will guide future research in the design of novel TZD derivatives by highlighting the general modifications conducted on the structure component of TZD scaffold affecting their potency, binding efficacy, and selectivity for the control of T2DM.

Background: The over use of current antibiotics and low discovery rate of the new ones are leading to rapid development of multidrug-resistant pathogens worldwide. Antimicrobial peptides have shown promising results against multidrug-resistant bacteria.Objective: To investigate the antimicrobial activity of a new ultrashort hexapeptide (OW).Methods: The OW hexapeptide was designed and tested against different strains of bacteria with different levels of sensitivity. Bacterial susceptibility assays were performed according to the guidelines of the Clinical and Laboratory Institute (CLSI). The synergistic studies were then conducted using the Checkerboard assay. This was followed by checking the hemolytic effect of the hexapeptide against human blood cells and Human Embryonic Kidney cell line (HEK293). Finally, the antibiofilm activities of the hexapeptide were studied using the Biofilm Calgary method.Results: Synergistic assays showed that OW has synergistic effects with antibiotics of different mechanisms of action. It showed an outstanding synergism with Rifampicin against methicillin resistant Staphylococcus aureus; ΣFIC value was 0.37, and the MIC value of Rifampicin was decreased by 85%. OW peptide also displayed an excellent synergism with Ampicillin against multidrug-resistant Pseudomonas aeruginosa, with ΣFIC value of less than 0.38 and a reduction of more than 96% in the MIC value of Ampicillin.Conclusion: This study introduced a new ultrashort peptide (OW) with promising antimicrobial potential in the management of drug-resistant infectious diseases as a single agent or in combination with commonly used antibiotics. Further studies are needed to investigate the exact mechanism of action of these peptides.