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Background: The search for novel antimicrobial agents effective against the emerging resistant pathogenic microorganisms to the currently used drugs is a substantial need. Herein, a novel series of compounds bearing a benzothiazolotriazole scaffold was synthesized and evaluated as potential antimicrobial agents against a panel of gram +ve, gram -ve bacteria, and fungi species. Methods: The new compounds were synthesized via hybridization between the benzothiazolotriazole scaffold and thiadiazole ring or various substituted aromatic moieties using the tethering technique in drug discovery. Results: The in vitro results revealed that these compounds have significant antifungal activity rather than antibacterial potential due to their high similarity with tricyclazole. Compound 7b bearing bromo-phenyl moiety was the most potent derivative with an MIC value of 8 μg/mL against Candida albicans and Penicillium chrysogenum. Conclusion: Collectively, benzothiazolotriazole-based derivatives are good antifungal leads and should be further actively pursued to expand treatment options for systemic and topical fungal infections.

1,3,4-Oxadiazole moiety is a crucial pharmacophore in many biologically active compounds. In a typical synthesis, probenecid was subjected to a sequence of reactions to obtain a 1,3,4-oxadiazole–phthalimide hybrid (PESMP) in high yields. The NMR (1H and 13C) spectroscopic analysis initially confirmed the structure of PESMP. Further spectral aspects were validated based on a single-crystal XRD analysis. Experimental findings were confirmed afterwards by executing a Hirshfeld surface (HS) analysis and quantum mechanical computations. The HS analysis showed the role of the π⋯π stacking interactions in PESMP. PESMP was found to have a high stability and lower reactivity in terms of global reactivity parameters. α-Amylase inhibition studies revealed that the PESMP was a good inhibitor of α-amylase with an s value of 10.60 ± 0.16 μg/mL compared with that of standard acarbose (IC50 = 8.80 ± 0.21 μg/mL). Molecular docking was also utilized to reveal the binding pose and features of PESMP against the α-amylase enzyme. Via docking computations, the high potency of PESMP and acarbose towards the α-amylase enzyme was unveiled and confirmed by docking scores of −7.4 and −9.4 kcal/mol, respectively. These findings shine a new light on the potential of PESMP compounds as α-amylase inhibitors.

In our previous work, it was reported that thymoquinone (TQ) and some thymohydroquinone (THQ) derivatives were used as precursors for the synthesis of potential anticancer agents. Hence, as a part of our ongoing program in the design of biologically active compounds derived from TQ scaffold we herein investigated the synthesis of homo- and heteronuclear thymol dimers tethered through various linkers such as ethylene, butylene, acetyl and N,N’-acetyl piperazine groups. The newly prepared compounds were examined as antimicrobial agents. Compounds 7 and 8 bearing a piperazine moiety exhibited highest antibacterial activity comparing to TQ, THQ and ampicillin especially against Staphylococcus aureus bacteria with MIC value of 16 µg/mL. All compounds showed moderate antifungal activity against Candida albicans and Aspergillus fumigatus. Together, the new TQ-based bivalent lead might be serving as a promising scaffold for development of novel and potent antimicrobial agents.

Endophytes are considered as a rich source of bioactive natural products. Many plants have not been investigated for their endophytic content yet, such as the medicinal plant Ficus carica. Recent studies confirmed antimicrobial and anticancer activities for the plant extract. To find out if its endophytes contribute to its reported activities, the bioactive endophyte Aspergillus neoniger was selected for investigation of its metabolites since it exerted antimicrobial and anticancer activities in preliminary screening assays. The fungal extract was subjected to bioactivity guided chromatographic fractionation for isolation of its bioactive metabolites. This resulted in the identification of four aurasperones (asperpyrone D, aurasperone D, dianhydroaurasperone C, aurasperone A) through spectroscopic analysis. Aurasperone D and asperpyrone D were found to be cytotoxic against human cervical cancer cells (50 % cytotoxic concentration=4.4 μg ml-1 and 3.0 μg ml-1 respectively). Aurasperone D exerted strong antiproliferative effect against human immortal erythroleukaemia cells 562 and human umbilical vein endothelial cells (concentration at which 50 % growth inhibition achieved is 5.3 and 4.7 μg ml-1) as well as asperpyrone D (concentration at which 50 % growth inhibition achieved is 4.9 and 5.4 μg ml-1). Dianhydroaurasperone C and aurasperone A, on the contrary, showed weak cytotoxic and antiproliferative effects. All compounds were tested for antimicrobial activity against several test strains including the plant pathogen Fusarium oxysporum. Results revealed that aurasperone D and asperpyrone D to be most active which suggests potential protective role of this endophyte on its host plant. These results suggest possible partial contribution of Aspergillus neoniger to the reported activity of the host plant

In the current study, we report the synthesis and cytotoxic evaluation of a new series of S-benzo[4,5]thiazolo[2,3-c][1,2,4]triazole-based derivatives 8-12. Cytotoxicity of the new compounds was investigated in A549, MCF-7, and Hep3B cancer cell lines. Among these derivatives, compound 12 bearing an isatin moiety was the most active derivative (IC50 = 2.40-3.53 µM). A mechanistic study of compound 12 was performed using the kinase profiling test to explore its inhibitory activity against 10 types of the oncogenic kinases and the potential activation of caspase 3/7 enzymes. The results revealed that compound 12 showed moderate inhibition of the EGFR and LCK kinases. Moreover, compound 12 also activated caspase-3/7 in A549 cells. The docking study of compound 12 into EGFR ATP-active site revealed that it fits nicely with good binding affinity. Together, the results indicated that compound 12 could serve as a good lead for developing new potential anticancer agents.

The main objective of this research work was the development and evaluation of transfersomes integrated oral films for the bioavailability enhancement of Ebastine (EBT) to treat allergic rhinitis. The flexible transfersomes, consisting of drug (EBT), lipid (Phosphatidylcholine) and edge activator (EA) Polyoxyethylene sorbitan monooleate or Sorbitan monolaurate, were prepared with the conventional thin film hydration method. The developed transfersomes were further integrated into oral films using the solvent casting method. Transfersomes were evaluated for their size distribution, surface charge, entrapment efficiency (EE%) and relative deformability, whereas the formulated oral films were characterized for weight, thickness, pH, folding endurance, tensile strength, % of elongation, degree of crystallinity, water content, content uniformity, in vitro drug release and ex vivo permeation, as well as in vivo pharmacokinetic and pharmacodynamics profile. The mean hydrodynamic diameter of transfersomes was detected to be 75.87 ± 0.55 nm with an average PDI and zeta potential of 0.089 ± 0.01 and 33.5 ± 0.39 mV, respectively. The highest deformability of transfersomes of 18.52 mg/s was observed in the VS-3 formulation. The average entrapment efficiency of the transfersomes was about 95.15 ± 1.4%. Transfersomal oral films were found smooth with an average weight, thickness and tensile strength of 174.72 ± 2.3 mg, 0.313 ± 0.03 mm and 36.4 ± 1.1 MPa, respectively. The folding endurance, pH and elongation were found 132 ± 1, 6.8 ± 0.2 and 10.03 ± 0.4%, respectively. The ex vivo permeability of EBT from formulation ETF-5 was found to be approximately 2.86 folds higher than the pure drug and 1.81 folds higher than plain film (i.e., without loaded transfersomes). The relative oral bioavailability of ETF-5 was 2.95- and 1.7-fold higher than that of EBT-suspension and plain film, respectively. In addition, ETF-5 suppressed the wheal and flare completely within 24 h. Based on the physicochemical considerations, as well as in vitro and in vivo characterizations, it is concluded that the highly flexible transfersomal oral films (TOFs) effectively improved the bioavailability and antihistamine activity of EBT.

The current study evaluated the immunomodulatory effects of Carica papaya pulp and seeds methanol (MeOH) extracts on mice infected with Listeria monocytogenes. Gas chromatography-mass spectrometry analysis identified 10 active constituents in C. papaya seed MeOH extract and 10 compounds in C. papaya pulp MeOH extract. The experimental animals were divided into negative control (G1) group, positive control (G2) group, pulp extract treated (G3) group, and seed extract treated (G4) group. After infection of animals (G2, G3, and G4), treatments were started for 3 weeks. Estimation of the immunological parameters showed a marked decrease in IgM levels and an increase in IgG levels in the treated groups (G3 and G4) compared with those in G2. The proinflammatory cytokines (IL-10, IL-12, IL-1β, IL-6, and TGF-β1) were decreased in the treated groups (G3 and G4) compared with those in G2. Nitric oxide levels were also decreased, and the percentages of phagocytosis increased compared with those of G2. The results demonstrated the immunomodulatory and anti-inflammatory effects of C. papaya pulp and seeds MeOH extracts. PRACTICAL APPLICATIONS: Based on the antioxidant and antibacterial activities exhibited by the pulp and seed MeOH extracts investigated in this study, Carica papaya might be considered as a natural source of phytochemicals that could be utilized in novel foods and pharmaceuticals. Further investigation are needed to identify and purify compounds that might be responsible for the observed effects.

The molecule of the title compound, C26H17ClFN3OS, comprises benzofuranyl (A), thiazolyl (B), pyrazolyl (C), chlorophenyl (D) and fluorophenyl (E) ring systems. Rings A–D are almost coplanar, as indicated by the twist angles between the ring pairs A/B, B/C and C/D of 7.6 (1), 4.7 (1) and 6.9 (2)°, respectively. Ring E is twisted by 73.2 (1)° from the plane through ring C. In the crystal, pairwise C—H...F interactions link the molecules into inversion dimers. Aromatic π–π interactions are also observed between rings A and E and between rings B and C for neighbouring pairs of molecules related by inversion symmetry. Taken together, the weak interactions generate [010] chains.

The asymmetric unit of the title compound, C20H17N5O, consists of two independent molecules. The molecules comprise tolyl (A), triazolyl (B), pyrazolecarbaldehydyl (C) and phenyl (D) groups. The angles between the planes through neighouring rings A/B, B/C and C/D are 39.1 (1), 6.0 (1) and 12.6 (1)°, respectively, for the first molecule and 46.0 (1), 4.6 (1) and 8.5 (2)°, respectively, for the second. In the crystal, the two independent molecules form dimers linked by four C—H...O hydrogen bonds with each O atom accepting two such links.

The title compound, C27H17ClFN3O2S, comprises chromonyl (A), thiazolyl (B), pyrazolyl (C), chlorophenyl (D) and fluorophenyl (E) rings with twist angles between the planes of adjacent rings pairs A/B, B/C, C/D and C/E of 14.1 (1), 18.2 (2), 1.3 (1) and 4.9 (1)°, respectively. The crystal structure is characterized by a range of intermolecular interactions including C—H...F, C—H...Cl and C—H...O contacts. Aromatic π–π stacking between chromonyl groups and chlorophenyl groups [centroid–centroid separations = 3.7170 (16) and 4.017 (2) Å, respectively] lead to columns of molecules propagating parallel to the [100] direction.

Ten new pyridine linked various substituted thiazole hybrids through (hydrazonomethyl)phenoxy-acetamide spacer were synthesized. The synthetic strategy was based on the reaction of the precursor 2-(4-((2-carbamothioylhydrazono)methyl)phenoxy)-N-(pyridin-2-yl)acetamide (3) with various α-halogenated carbonyl compounds (namely; phenacyl bromides, ethyl bromoacetate, diethyl bromomalonate and 3-chloropentane-2,4-dione). Moreover, the cytotoxicity properties of the synthesized compounds have been studied against liver carcinoma (HepG2), laryngeal carcinoma (Hep-2), prostate cancer (PC3), breast cancer (MCF-7) and normal fibroblast cells (WI38). The pyridine-thiazole compounds 7 and 10 revealed promising anticancer activity against MCF-7 and HepG2 cell lines with IC50 values in the range 5.36–8.76 μM compared to the activity of 5-fluorouracil. Docking study provided valuable insights for binding sites of the synthesized compounds with Rho-associated protein kinase (ROCK-1).

A novel set of S-benzo[4,5]thiazolo[2,3-c][1,2,4]triazoles was synthesized. Cytotoxicity of these compounds was evaluated against three cancer cell lines of different origins, Hep3B, A549, and MCF-7. Three of these compounds were screened by NCI for growth inhibitory activities against 60 cancer cell lines. The results revealed significant cytotoxic activities for compounds 13a-i. Among these derivatives, compounds 13c and 13f-13i exhibited the highest cytotoxicity against the selected cancer cell lines with IC50 values between 3.17 and 14.18 μM. The structure-activity relationship of compounds 13a-i indicated favorable cytotoxic results on the expansion of the cyclic amine and the substitution with aminothiazole moiety. A mechanistic study revealed the activation of caspase-3/7 in A549 cells on treatment with compounds 13f-i at 5–20 μM. Moreover, the results of flow cytometric analysis suggested that compound 13i efficiently induced apoptosis in a dose-dependent manner. Compounds 13f,g,i also exhibited a weak to moderate inhibition of multiple kinases where compound 13i was the most active in inhibiting the activity of CDK2/Cyclin A1 (IC50 = 4.65 μM). The current work provided a novel set of compounds with cytotoxic, kinase inhibition, and apoptosis-inducing activities, which can serve as a lead for further optimization.