Synthesis of pyrazinamide analogues and their antitubercular bioactivity

Wati, First Ambar; Adyarini, Prisna U.; Fatmawati, Sri; Santoso, Mardi

doi:10.1007/s00044-020-02626-0

Cited by 11 publications

(16 citation statements)

References 20 publications

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“…The different chloropyrazine-tethered pyrimidine derivatives (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) were obtained by the condensation of chloropyrazinyl chalcones (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) with guanidine hydrochloride (Scheme 1) using a base catalyst (KOH) in yields ranging from 56-92%. The molecular structures of the chloropyrazine-tethered pyrimidine hybrids were disentangled using FT-IR and 1 H NMR spectral data and are presented in our previous paper [55].…”

Section: Chemistrymentioning

confidence: 99%

“…Among these three, the analogue 25 bearing a 4″-nitro group was most active with an MIC of 48.6 µ M. Replacement of the nitro group at the para position by chlorine and fluorine atoms in compounds 23 and 24 decreased the antibacterial activity compared with 25. On the other hand, the presence of electron-donating groups in position-4″ of the phenyl ring (26)(27)(28)(29) appeared to be detrimental for antibacterial activity. The numbers in bold designate the activity of the compounds with more potency than the reference standard.…”

Section: Antibacterial Activitymentioning

confidence: 99%

“…Examples of drugs with a pyrimidine nucleus are antibacterial and antimalarial agents targeting the folate pathway: trimethoprim, iclaprim, sulfadimethoxine, pyrimethamine, and sulfadoxine; antimetabolite and ergosterol biosynthesis inhibitor antifungal drugs: flucytosine and voriconazole; antimetabolite anti-cancer agents: 5-fluorouracil and capecitabine; tyrosine kinase inhibitors: imatinib, dasatinib, and nilotinib; antivirals: ara-c, idoxuridine, zidovudine, stavudine, lamivudine, and emtricitabine; and the antitubercular drug capreomycin (Figure 1). Many substituted pyrazine derivatives were reported with potential antibacterial [6][7][8][9][10][11], antifungal [12][13][14][15], anticancer [16][17][18][19][20][21], antioxidant [22][23][24][25], and antitubercular [9,[26][27][28] activities. Similarly, pyrimidine-based compounds also showed excellent antimicrobial (antibacterial and antifungal) [29][30][31][32][33], antimycobacterial [34][35][36][37][38], antioxidant [39][40][41][42], cytotoxic and anticancer [42][43][44]…”

Section: Introductionmentioning

confidence: 99%

“…In our previous study, we reported the antimicrobial and antiproliferative activities of chloropyrazine-linked 1,5-benzothiazepine hybrids [54]. Considering the significant biological activities of pyrimidine derivatives, previously we synthesized and evaluated the antitubercular activity of chloropyrazine-tethered pyrimidine hybrids (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) [55]. These derivatives (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) are analogues of chloropyrazine-linked 1,5-benzothiazepine hybrids where the pyrimidine ring replaces the 1,5-benzothiazepine motif with the other parts of the compounds being the same (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

“…Considering the significant biological activities of pyrimidine derivatives, previously we synthesized and evaluated the antitubercular activity of chloropyrazine-tethered pyrimidine hybrids (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) [55]. These derivatives (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) are analogues of chloropyrazine-linked 1,5-benzothiazepine hybrids where the pyrimidine ring replaces the 1,5-benzothiazepine motif with the other parts of the compounds being the same (Figure 2). Here, we report the antimicrobial as well as the antiproliferative activities of chloropyrazine-tethered pyrimidine hybrids with the aim to develop potent antimicrobial and antiproliferative hybrids.…”

Section: Introductionmentioning

confidence: 99%

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Assessment of the Antimicrobial and Antiproliferative Activities of Chloropyrazine-Tethered Pyrimidine Derivatives: In Vitro, Molecular Docking, and In-Silico Drug-Likeness Studies

Bhandare

Shaik

2021

Applied Sciences

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Molecular hybridization (MH) of heterocyclic rings has enabled scientists to design and develop novel drugs and drug-like candidates. In our previous work, considering the importance of MH, we synthesized different kinds of chloropyrazine-tethered pyrimidine derivatives (22–40) containing either substituted phenyl or heteroaryl rings at position-6 of the pyrimidine ring and evaluated their antitubercular activity. Herein, we report the antimicrobial and antiproliferative activities of 22–40. The antiproliferative activity of the target hybrids was superior to the antimicrobial activity. However, some compounds showed greater antimicrobial activity than the standard drugs. For instance, among the nineteen derivatives, compound 31 containing a 2″,4″-dichlorophenyl ring, showed the most potent antibacterial and antifungal activities (MIC 45.37 µM), followed by compounds 25 and 30 bearing 4″-nitrophenyl and 2″,4″-difluorophenyl scaffolds with minimum inhibitory concentrations (MIC) values of 48.67 µM and 50.04 µM, respectively. Compound 35, containing a bioisosteric 2″-pyridinyl ring, showed the most potent antiproliferative activity against the prostate cancer cell line (DU-145) with an IC50 value of 5 ± 1 µg/mL. Additional testing of compounds 22–40 on human normal liver cells (LO2) indicated that the compounds were more selective to cancer cell lines over normal cells. Further, molecular docking of the most potent compound 35 against dihydrofolate reductase (DHFR) (PDB ID: 1U72) had a good binding affinity with a docking score of −6.834. The SwissADME program estimated the drug-likeness properties of compound 35. Hybrid 35 is a potential lead molecule for the development of new anticancer drugs, whereas 31 is a promising antimicrobial lead candidate.

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Section: Chemistrymentioning

confidence: 99%

Section: Antibacterial Activitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Assessment of the Antimicrobial and Antiproliferative Activities of Chloropyrazine-Tethered Pyrimidine Derivatives: In Vitro, Molecular Docking, and In-Silico Drug-Likeness Studies

Bhandare

Shaik

2021

Applied Sciences

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Repurposing antiparasitic N,N′‐aliphatic diamine derivatives as promising antimycobacterial agents

Recio‐Balsells,

Carlucci,

Giovannuzzi

et al. 2024

Archiv der Pharmazie

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In previous studies, we demonstrated the potent activity of a library of 25 N,N′‐disubstituted diamines (NNDDA) toward Trypanosomatid and Apicomplexa parasites. Considering the structure similarity between this collection and SQ109, an antituberculosis compound, and its compelling antiparasitic properties, we aimed to repurpose this library for tuberculosis treatment. We assayed this collection against Mycobacterium tuberculosis H37Rv and M. avium, obtaining several compounds with MIC values below 10 µM. The most active analogs were also evaluated against M. smegmatis, a non‐pathogenic species, and the non‐tuberculosis mycobacteria M. abscessus, M. kansasii, and M. fortuitum. 3c stands out as the lead mycobacterial compound of the collection, with potent activity against M. tuberculosis (minimal inhibitory concentration [MIC] = 3.4 µM) and moderate activity against M. smegmatis, M. kansasii, and M. fortuitum (all with MIC values of 26.8 µM). To unravel the mechanism of action, we employed the web‐based platform Polypharmacology Browser 2 (PPB2), obtaining carbonic anhydrases as potential drug targets. Nevertheless, none of the compounds displayed experimental inhibition. In summary, our study confirms the validity of the repurposing approach and underscores the antimycobacterial potential of NNDDA compounds, especially the analog 3c, setting a stepping stone for further studies.

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Synthesis, α-glucosidase inhibitory activity, and molecular docking of cinnamamides

et al. 2023

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Synthesis of pyrazinamide analogues and their antitubercular bioactivity

Cited by 11 publications

References 20 publications

Assessment of the Antimicrobial and Antiproliferative Activities of Chloropyrazine-Tethered Pyrimidine Derivatives: In Vitro, Molecular Docking, and In-Silico Drug-Likeness Studies

Assessment of the Antimicrobial and Antiproliferative Activities of Chloropyrazine-Tethered Pyrimidine Derivatives: In Vitro, Molecular Docking, and In-Silico Drug-Likeness Studies

Repurposing antiparasitic N,N′‐aliphatic diamine derivatives as promising antimycobacterial agents

Synthesis, α-glucosidase inhibitory activity, and molecular docking of cinnamamides

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