In this study, a series of novel benzofuran-based 1,2,4-triazole derivatives (10a–e) were synthesized and evaluated for their inhibitory potential against acetylcholinesterase (AChE) and bacterial strains (E. coli and B. subtilis). Preliminary results revealed that almost all assayed compounds displayed promising efficacy against AChE, while compound 10d was found to be a highly potent inhibitor of AChE. Similarly, these 5-bromobenzofuran-triazoles 10a–e were screened against B. subtilis QB-928 and E. coli AB-274 to evaluate their antibacterial potential in comparison to the standard antibacterial drug penicillin. Compound 10b was found to be the most active among all screened scaffolds, with an MIC value of 1.25 ± 0.60 µg/mL against B. subtilis, having comparable therapeutic efficacy to the standard drug penicillin (1 ± 1.50 µg/mL). Compound 10a displayed excellent antibacterial therapeutic efficacy against the E. coli strain with comparable MIC of 1.80 ± 0.25 µg/mL to that of the commercial drug penicillin (2.4 ± 1.00 µg/mL). Both the benzofuran-triazole molecules 10a and 10b showed a larger zone of inhibition. Moreover, IFD simulation highlighted compound 10d as a novel lead anticholinesterase scaffold conforming to block entrance, limiting the swinging gate, and disrupting the catalytic triad of AChE, and further supported its significant AChE inhibition with an IC₅₀ value of 0.55 ± 1.00 µM. Therefore, compound 10d might be a promising candidate for further development in Alzheimer’s disease treatment, and compounds 10a and 10b may be lead antibacterial agents.

The tyrosinase enzyme has a vital role in the browning of vegetables and fruits and the biosynthesis of melanin. In this work, we synthesized a diverse library of coumarin–triazole hybrids, and these compounds were characterized by using suitable analytical techniques. Our research work extends beyond the synthetic effort to explore the therapeutic potential of these compounds. We put the synthesized compounds through meticulous in vitro screening against the tyrosinase enzyme, and these coumarin derivatives evinced good IC₅₀ values in the range of 0.339 ± 0.25 µM to 14.06 ± 0.92 µM. In the library of synthesized compounds, six compounds were found to be more potent than standard ascorbic acid (IC₅₀ = 11.5 ± 1.00), and among them, 17e and 17f, being the most active, exhibited remarkable anti-tyrosinase potential, with IC₅₀ values of 0.339 ± 0.25 μM and 3.148 ± 0.23 μM, respectively. Furthermore, an in silico modeling study was carried out to determine the key interactions of these compounds with the tyrosinase protein (PDB ID: 2Y9X) and thus to authenticate our experimental findings. The quantitative SAR studies exhibited a good correlation between the synthesized derivatives of coumarin and their anti-tyrosinase activity. The docking studies verified the experimental results, and ligand 17e showed good interaction with the core residues of tyrosinase. This study not only expands the field of coumarin–triazole hybrid synthesis but also provides valuable insights for the development of novel tyrosinase inhibitors.

Piperazine is a privileged moiety that is a structural part of many clinical drugs. Piperazine-based scaffolds have attracted the attention of pharmaceutical and medicinal scientists to develop novel, efficient therapeutic agents owing to their significant and promising biological profile. In the current study, an ecofriendly ultrasonic-assisted synthetic approach was applied to achieve a novel series of 1-tosyl piperazine dithiocarbamate acetamide hybrids 4a–4j, which was evaluated for in vitro tyrosinase inhibition and thrombolytic and hemolytic cytotoxic activities. Among all the piperazine-based dithiocarbamate acetamide target molecules 4a–4j, the structural analogs 4d displayed excellent tyrosinase inhibition efficacy (IC₅₀ = 6.88 ± 0.11 µM) which was better than the reference standard drugs kojic acid (30.34 ± 0.75 µM) and ascorbic acid (11.5 ± 1.00 µM), respectively, which was further confirmed by in silico induced-fit docking (IFD) simulation Good tyrosinase activities were exhibited by 4g (IC₅₀ = 7.24 ± 0.15 µM), 4b (IC₅₀ = 8.01 ± 0.11 µM) and 4c (IC₅₀ = 8.1 ± 0.30 µM) dithiocarbamate acetamides, which were also better tyrosinase inhibitors than the reference drugs but were less active than the 4d structural hybrid. All the derivatives are less toxic, having values in the 0.29 ± 0.01% to 15.6 ± 0.5% range. The scaffold 4b demonstrated better hemolytic potential (0.29 ± 0.01%), while a remarkably high thrombolytic chemotherapeutic potential was displayed by analog 4e (67.3 ± 0.2%).

The therapeutic potential of whitish glaucous sub-shrub Haloxylon griffithii (H. griffithii), abundantly present in southern regions of South Asia, has been neglected. The current study aimed to assess the phytochemicals and pharmacological potential of native and gemm forms of H. griffithii. Results of antimicrobial activity revealed that all tested bacteria were susceptible at concentrations ≤50 µg/mL, while tested fungal species were susceptible at ≤25 µg/mL. The values of minimum bactericidal concentrations (MBCs) ranged between 10.75 ± 0.20 to 44.25 ± 0.42 µg/mL, 8.25 ± 0.02 to 28.20 ± 0.80 µg/mL. The value of minimum inhibitory concentration (MIC) of all microbial species was ≤100 µg/mL and the antibiotic mechanism showed that both extracts were highly bactericidal and fungicidal. Results of average log reduction of viable cell count in time kill assay indicated that Pseudomonas aeruginosa (P. aeruginosa) NCTC 1662, Candida albicans (C. albicans) IBL-01, Candidakrusei (C. krusei) ATCC 6258, and Aspergillus flavus (A. flavus) QC 6158 were the most susceptible microbial species. High performance liquid chromatography (HPLC)-based quantification confirmed the presence of gallic acid p.coumeric acid catechin, vanillin, ellagic acid, and salicylic acid, while in native extract only gallic acid. Native and gemm extracts exhibited excellent radical scavenging potential measured by 1,1-diphenyl-2-picryl-hydrazyl radical scavenging assay. Significant thrombolytic activity was found in both extracts with negligible haemolytic activity. Highest percent (%) clot lysis was observed with gemm extracts (87.9 ± 0.85% clot lysis). In summary, we infer that valuable evidence congregated can be exploited for better understanding of gemm H. griffithii’s health benefits, further, to increase its utility with enriching dietary sources of health-promoting compounds.