Synthesis, crystal structure and biological evaluation of some novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines

Khan, Imtiaz; Zaib, Sumera; Ibrar, Aliya; Rama, Nasim Hasan; Simpson, Jim; Iqbal, Jamshed

doi:10.1016/j.ejmech.2014.03.046

Cited by 87 publications

(49 citation statements)

References 42 publications

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“…33,34 The inhibitory activity results are summarized in Table 5 in the form of IC 50 values. 33,34 The inhibitory activity results are summarized in Table 5 in the form of IC 50 values.…”

Section: Carbonic Anhydrase Inhibitionmentioning

confidence: 99%

Exploiting the potential of aryl acetamide derived Zn(ii) complexes in medicinal chemistry: synthesis, structural analysis, assessment of biological profile and molecular docking studies

et al. 2016

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In the medical arena, advancements in the rational design of metal-based therapeutic agents showcase increasingly significant research attempts towards the development of new compounds with fewer toxic side effects. In this context, our present manuscript explicitly encapsulates the design and synthesis of Zn(II) complexes derived from different aryl acetamides, as potential frontline enzyme inhibitors as well as antileishmanial and anticancer agents. The structures of synthesized metal complexes were established on the basis of spectro-analytical data and, in case of 4c, by single crystal X-ray diffraction analysis. The X-ray structure of Zn(II) complex, dichlorido-bis[N-(4-methoxyphenyl)acetamide-O]-zinc(II), 4c, showed the zinc atom and the chlorido ligands to lie on a mirror plane with the acetamide ligands in general positions. The coordination geometry of the zinc atom was tetrahedral with the N-(4-methoxyphenyl)acetamide ligands bound to zinc via the acetamide oxygens. The designed coordination complexes were analysed for their enzyme inhibition potential, anticancer and antileishmanial efficacy. Detailed kinetics studies for complex 4b, the most active carbonic anhydrase and alkaline phosphatase inhibitor, indicated a competitive and uncompetitive mode of inhibition against carbonic anhydrase and tissue non-specific alkaline phosphatase, respectively. The bioactivity results and molecular docking analysis revealed that the synthesized coordination complexes (4a-c) hold great potential to be developed as promising enzyme inhibitors in addition to the anticancer and anti-parasitic drug candidates. disorders. 1 In this quest, several coordination compounds have been synthesized involving different metal center like copper, zinc, cobalt, nickel, gold and antimony. 2,3 In addition, a variety of mononuclear metal complexes with different ligands have been shown to be effective for cancer therapy both in vitro and in vivo. 4-8 Transition metal complexes with platinum, gold, palladium and ruthenium metal centers are under various stages of clinical trials. 9,10 Interest in zinc complexes stems from their wide and increasing utility in medicinal chemistry. In addition, zinc is considered as the most abundant trace intracellular element with its substantial occurrence in the nucleus. 11 Furthermore, Zn(II) ions are present in zinc finger proteins that recognize and bind to DNA. 12,13 Several Zn(II) and other metal complexes with a variety of ligands have been reported in the literature with different coordination modes displaying a unique spectrum of biological functions including antitumor, antioxidant, xanthine oxidase, anticonvulsant, antimicrobial and antileishmanicidal activities. 14 Also, various metal complexes with different coordination ligands have emerged as inhibitors of carbonic anhydrases, 15 cholinesterase, 16 and alkaline phosphatases. 17 However, there is still an unmet need for the development of coordination complexes with unique and multifaceted biological profile.Hence, a combination of all com...

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“…33,34 The inhibitory activity results are summarized in Table 5 in the form of IC 50 values. 33,34 The inhibitory activity results are summarized in Table 5 in the form of IC 50 values.…”

Section: Carbonic Anhydrase Inhibitionmentioning

confidence: 99%

Exploiting the potential of aryl acetamide derived Zn(ii) complexes in medicinal chemistry: synthesis, structural analysis, assessment of biological profile and molecular docking studies

et al. 2016

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“…Heterocyclic fused ring systems consisting of 1,2,4‐triazole or 1,3,4‐thiadiazine represent a class of compounds that possess a broad spectrum of biological activities such as anti‐inflammatory, antiviral, antimicrobial, and antitumor activity .…”

Section: Introductionmentioning

confidence: 99%

An Easy Access to Construct Some New Fused 1,2,4‐Triazines with Ring Junction Nitrogen Systems and Their Biological Evaluation

Hamama

El‐Bana

Shaaban

et al. 2016

Journal of Heterocyclic Chem

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The chemical reactivity of 4‐amino‐6‐benzyl‐3‐mercapto‐1,2,4‐triazine‐5(4H)‐one (1) towards various aliphatic or/and mono and bis aromatic carboxylic acid derivatives to give the corresponding fused heterocyclic systems, 1,3,4‐thiadiazoles 4, 5, 6, which incorporating 1,2,4‐triazine moiety was achieved. Moreover, compound 1 was subjected to reaction either with halo acetic acids or bromo ester to afford the respective fused nitrogen ring junction systems, thiadiazole 2 and 3 or thiadiazine 7. However, while the tetracyclic ring system 9 was furnished through condensation reaction of isatine with triazine 1. In addition, some of the new synthesized compounds were evaluated as an antioxidant and antitumor agents.

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“…Therefore, one of the most important strategies in AD treatment is to restore the levels of ACh by inhibiting ChE enzymes . There are two types of ChE enzymes: acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8).…”

Section: Introductionmentioning

confidence: 99%

Novel cinnamic acid–tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study

Ghafary

Najafi

Mohammadi-Khanaposhtani

et al. 2018

Archiv der Pharmazie

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A novel series of cinnamic acid–tryptamine hybrids was designed, synthesized, and evaluated as cholinesterase inhibitors. Anticholinesterase assays showed that all of the synthesized compounds displayed a clearly selective inhibition of butyrylcholinesterase (BChE), but only a moderate inhibitory effect toward acetylcholinesterase (AChE) was detected. Among these cinnamic acid–tryptamine hybrids, compound 7d was found to be the most potent inhibitor of BChE with an IC50 value of 0.55 ± 0.04 μM. This compound showed a 14‐fold higher inhibitory potency than the standard drug donepezil (IC50 = 7.79 ± 0.81 μM) and inhibited BChE through a mixed‐type inhibition mode. Moreover, a docking study revealed that compound 7d binds to both the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of BChE. Also, compound 7d was evaluated against β‐secretase, which exhibited low activity (inhibition percentage: 38%).

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Synthesis, crystal structure and biological evaluation of some novel 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines

Cited by 87 publications

References 42 publications

Exploiting the potential of aryl acetamide derived Zn(ii) complexes in medicinal chemistry: synthesis, structural analysis, assessment of biological profile and molecular docking studies

Exploiting the potential of aryl acetamide derived Zn(ii) complexes in medicinal chemistry: synthesis, structural analysis, assessment of biological profile and molecular docking studies

An Easy Access to Construct Some New Fused 1,2,4‐Triazines with Ring Junction Nitrogen Systems and Their Biological Evaluation

Novel cinnamic acid–tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study

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