Synthesis of novel antibacterial and antifungal dithiocarbamate-containing piperazine derivatives via re-engineering multicomponent approach

Halimehjani, Azim Ziyaei; Dehghan, Faezeh; Tafakori, Vida; Amini, Elaheh; Hooshmand, Seyyed Emad; Nosood, Yazdanbkhsh Lotfi

doi:10.1016/j.heliyon.2022.e09564

Cited by 11 publications

(3 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to their substantial applications across industries, including biological, agricultural, medicinal and pharmacological fields, chemists have drawn their attention to various heterocyclic scaffolds, such as piperazines (Halimehjani et al, 2022), benzoxazole, benzothiazole (Zou et al, 2023), heterocyclic sulfonamides (Apiraksattayakul et al, 2022), benzofurans (Farhat et al, 2022), benzimidazoles (Nardi et al, 2023), thiadiazoles (Janowska et al, 2020), pyarzoles (Nazeer et al, 2023), lamivudines (Henriquez-Camacho et al, 2023), ciprofloxacin-based acetanilides (Zhang et al, 2018), triazoles (Irfan et al, 2024), quinoxalines (Montana et al, 2019), and oxadiazoles (Kerru et al, 2020;Irfan et al, 2022;Irfan et al, 2023). Notably, theophylline (Shahzadi et al, 2020;Shahzadi et al, 2022a), a naturally occurring methylxanthine, has found frequent therapeutic use in treating conditions such as asthma, respiratory deficits in premature infants, and chronic pulmonary obstructive disease (COPD).…”

Section: Introductionmentioning

confidence: 99%

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

Saeed,

Shahzadi,

Zahoor

et al. 2024

Front. Chem.

View full text Add to dashboard Cite

Theophylline, a nitrogen-containing heterocycle, serves as a promising focal point for medicinal researchers aiming to create derivatives with diverse pharmacological applications. In this work, we present an improved synthetic method for a range of theophylline-1,2,4-triazole-S-linked N-phenyl acetamides (4a‒g) utilizing ultrasound-assisted synthetic approach. The objective was to assess the effectiveness of synthesized theophylline-1,2,4-triazoles (4a‒g) as inhibitors of HCV serine protease and as antibacterial agents against B. subtilis QB-928 and E. coli AB-274. Theophylline-1,2,4-triazoles were obtained in good to excellent yields (69%–95%) in a shorter time than conventional approach. 4-Chlorophenyl moiety containing theophylline-1,2,4-triazole 4c displayed significantly higher inhibitory activity against HCV serine protease enzyme (IC50 = 0.015 ± 0.25 mg) in comparison to ribavirin (IC50 = 0.165 ± 0.053 mg), but showed excellent binding affinity (−7.55 kcal/mol) with the active site of serine protease, better than compound 4c (−6.90 kcal/mol) as well as indole-based control compound 5 (−7.42 kcal/mol). In terms of percentage inhibition of serine protease, 2-chlorophenyl compound 4b showed the maximum percentage inhibition (86%), more than that of the 3,4-dichlorophenyl compound 4c (76%) and ribavirin (81%). 3,4-Dimethylphenyl-based theophylline-1,2,4-triazole 4g showed the lowest minimum inhibitory concentration (MIC = 0.28 ± 0.50 μg/mL) against the B. subtilis bacterial strain as compared to the standard drug penicillin (MIC = 1 ± 1.50 μg/mL). The other 4-methylphenyl theophylline-1,2,4-triazole 4e (MIC = 0.20 ± 0.08 μg/mL) displayed the most potent antibacterial potential against E. coli in comparison to the standard drug penicillin (MIC = 2.4 ± 1.00 μg/mL). Molecular docking studies further helped in an extensive understanding of all of the interactions between compounds and the enzyme active site, and DFT studies were also employed to gain insights into the molecular structure of the synthesized compounds. The results indicated that theophylline-linked triazole derivatives 4b and 4c showed promise as leading contenders in the fight against the HCV virus. Moreover, compounds 4e and 4g demonstrated potential as effective chemotherapeutic agents against E. coli and B. subtilis, respectively. To substantiate these findings, additional in vivo studies and clinical trials are imperative, laying the groundwork for their integration into future drug design and development.

show abstract

Section: Introductionmentioning

confidence: 99%

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

Saeed,

Shahzadi,

Zahoor

et al. 2024

Front. Chem.

View full text Add to dashboard Cite

show abstract

“…The presence of nitrogen atoms makes piperazine basic which allows the medicinal chemist to utilize it as a building block for the development of newer bioactive molecules with a wide range of pharmacological potential (Sharma et al., 2020). Nowadays, various piperazine derivatives are discovered and have been used for several biological activities like antidepressant (Kumar et al., 2021), antipsychotic (Bari et al., 2021), anticancer (Al‐Ghorbani et al., 2022), antibacterial (Sanad & Mekky, 2020), antifungal (Halimehjani et al., 2022), antimicrobial (Yildiz, 2020), antimalarial (Nguyen et al., 2021), anti‐inflammatory (Jain et al., 2021), etc. Piperazine moiety is present in many commonly used medications that fall into different pharmacological classifications as shown in Figure 1 (Shaquiquzzaman et al., 2015).…”

Section: Introductionmentioning

confidence: 99%

The medicinal chemistry of piperazines: A review

Faizan,

Kumar,

Mazumder

et al. 2024

Chem Biol Drug Des

View full text Add to dashboard Cite

The versatile basic structure of piperazine allows for the development and production of newer bioactive molecules that can be used to treat a wide range of diseases. Piperazine derivatives are unique and can easily be modified for the desired pharmacological activity. The two opposing nitrogen atoms in a six‐membered piperazine ring offer a large polar surface area, relative structural rigidity, and more acceptors and donors of hydrogen bonds. These properties frequently result in greater water solubility, oral bioavailability, and ADME characteristics, as well as improved target affinity and specificity. Various synthetic protocols have been reported for piperazine and its derivatives. In this review, we focused on recently published synthetic protocols for the synthesis of the piperazine and its derivatives. The structure–activity relationship concerning different biological activities of various piperazine‐containing drugs has also been highlighted to provide a good understanding to researchers for future research on piperazines.

show abstract

“…Changes in molecular structure caused by limited stability will eventually change the microbial receptor as the final target, which, in turn, will lead to the adaptation of the acidic substance of the microbial nucleus as a defensive approach against changes in the chemical structure of drugs. These results in a phenomenon often described as AMR [ 7 – 9 ]. In this regard, the efforts to promote medicinal plant-based formulations will further minimize the AMR phenomenon.…”

Section: Introductionmentioning

confidence: 99%

Toxicity test of flavonoid compounds from the leaves of Dendrophthoe pentandra (L.) Miq. using in vitro culture cell models

et al. 2022

View full text Add to dashboard Cite

Background and Aim: The flavonoids from mistletoe are thought to have antimicrobial action. This encouraging finding supports the benefits of medicinal plants as a substitute for synthetic antimicrobials, thus promoting healthy lifestyles. In contrast, it is known that the use of topical drug formulations made from flavonoids of mistletoe (Dendrophthoe pentandra (L.) Miq. Loranthaceae) with Indonesian name, Benalu duku (BD) is required in skin cell irritation. This study aimed to assess the toxic effects of the flavonoid substances of BD, as an initial screening. Materials and Methods: A myeloma cell line was cultured in Roswell Park Memorial Institute medium, and the Baby Hamster Kidney clone 12 (BHK21) cell line was cultured in Dulbecco's Modified Eagle's Medium from stock (±9 × 107 cells/mL), and 1.2 mL of culture were distributed into each well of a microtiter plate. Subsequently, 0.2 mL of serially diluted flavonoid compounds (0.5–3 μg/mL) were added to 12 wells for each concentration, as trial groups (including control groups), followed by a 2-day incubation. Observations were performed based on the cytopathic effect (CPE) using an inverted microscope at a magnification of 100×. Results: Cytopathic effect was detected on the microtiter plate wells for the groups of myeloma and BHK21 cells at a flavonoid concentration of 0.5 μg/mL–3 μg/mL. Conclusion: Flavonoid compounds from BD were safely used for topical treatment of cancer cells at a concentration <2.491 μg/mL, whereas for non-cancerous cells, a concentration <2.582 μg/mL was sufficient (p < 0.05).

show abstract

Synthesis of novel antibacterial and antifungal dithiocarbamate-containing piperazine derivatives via re-engineering multicomponent approach

Cited by 11 publications

References 30 publications

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

Exploring theophylline-1,2,4-triazole tethered N-phenylacetamide derivatives as antimicrobial agents: unraveling mechanisms via structure-activity relationship, in vitro validation, and in silico insights

The medicinal chemistry of piperazines: A review

Toxicity test of flavonoid compounds from the leaves of Dendrophthoe pentandra (L.) Miq. using in vitro culture cell models

Contact Info

Product

Resources

About