Synthesis, docking, and evaluation of novel thiazoles for potent antidiabetic activity

Sravanthi, T. V.; Lulu, Sajitha; Vino, S; Jayasri, M. A.; Arumugam, Mohanapriya; Manju, S. L.

doi:10.1007/s00044-017-1851-8

Cited by 34 publications

(17 citation statements)

References 24 publications

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“…Therefore, analogues bearing thiazoles which are the NÀ S containing five membered heterocyclic ring structures coming under the group of azoles are one of the most privileged scaffolds in drug and remains of great importance, because of their potent biological activity against variety of diseases (Figure 1) such as Tiazofurin and Dasatinib (anticancer), Sulfathiazole (antimicrobial), Abafungin (anti-fungal), and Meloxicam (anti-inflammatory). [7] Even more, thiazole or thiazolyl scaffold showed multifunctional therapeutics effect from antimicrobial and antifungal, [8][9][10] to antitubercular, [11] anticancer, [12,13] anticandidal, [14] anti-HIV [15] and antidiabetic [16] agents. Also, pyrazoles, which are fivemembered heterocyclic rings containing two adjacent nitrogen possess a large spectrum of activity have been proved for their antimicrobials [17] and anticancer effect.…”

Section: Introductionmentioning

confidence: 99%

“…Even more, thiazole or thiazolyl scaffold showed multifunctional therapeutics effect from antimicrobial and antifungal, [8–10] to antitubercular, [11] anticancer, [12,13] anticandidal, [14] anti‐HIV [15] and antidiabetic [16] agents. Also, pyrazoles, which are five‐membered heterocyclic rings containing two adjacent nitrogen possess a large spectrum of activity have been proved for their antimicrobials [17] and anticancer effect [18,19] .…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Structure‐Activity Relationship and in silico Studies of Novel Pyrazolothiazole and Thiazolopyridine Derivatives as Prospective Antimicrobial and Anticancer Agents

et al. 2021

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In our attempt to develop potential new drug candidates with promising dual antimicrobial and anticancer activities, a series of pyrazolothiazole and thiazolopyridine analogues has been synthesized. All compounds were evaluated for their antimicrobial potential towards pathogenic strains and cytotoxicity properties against hepatic cancer cell line HepG-2 and breast cancer cell line MCF-7. 9 c showed excellent antimicrobial activity against the tested strains, with MIC values about 27.5 μM (S. epidermidis), 6.8 (B. subtilis) and 3.4 μM (S. pneumoniae and K. pneumoniae) fold higher than the reference drug, whilst 9 a, 9 b and 5 a exhibited also potent activity against selected strains. Moreover, compounds 9 c (IC50 = 10.89 μM and 15.60 μM) and 9 a (IC50 = 22.24 μM and 28.47 μM) showed promising anticancer activity for HepG2 and MCF-7 cell lines, respectively, when compared to the known anticancer drugs, 5-Fluorouracil (IC50 = 26.75 μM and IC50 = 32.75 μM). The data from structure-activity relationships analysis revealed the potency of pyrazolothiazole than thiazolopyridine derivatives in generating potential activity. Further, molecular docking studies performed on the more active antimicrobial and cytotoxic compound, 9 c to get insights for binding modes to the target enzymes (PDB ID: 1JIJ) for antimicrobial, and (PDB ID: 1DI8) and (PDB ID: 3TWJ) for anticancer revealed that they interacted with the same key amino acids with TyrRS for S. aureus, CDK2 and ROCK1, respectively.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis, Structure‐Activity Relationship and in silico Studies of Novel Pyrazolothiazole and Thiazolopyridine Derivatives as Prospective Antimicrobial and Anticancer Agents

et al. 2021

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“…Among them, 2-[5-(1H-indol-3-yl)-3-phenyl-1H-pyrazol-1-yl]-4-(4-bromophenyl)thiazole demonstrated better antihyperglycemic activity in comparison with the standard drug acarbose. 74 Aromatic pyrazoles can be obtained from indolylvinyl ketones directly, in one-pot manner. Thus, the cyclization of 1-phenyl-3-(2-phenyl-1H-indol-3-yl)prop-2-en-1-one with phenylhydrazine in 1,2-dichlorobenzene (ODCB) provided substituted indolylpyrazole 119 in 48% yield (Scheme 63).…”

Section: Scheme 60mentioning

confidence: 99%

Indolylvinyl Ketones: Building Blocks for the Synthesis of Natural Products and Bioactive Compounds

et al. 2019

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Indolylvinyl ketones are valuable building blocks that can be utilized for the synthesis of numerous natural products and bioactive molecules containing an indole core motif. Herein, we describe their application for the total synthesis of some alkaloids, their analogues, and a variety of other important compounds, with an emphasis on biologically active examples.1 Introduction2 Functionalization of the Enone C=C Bond2.1 Reduction2.2 Michael Addition2.3 Cycloaddition3 Transformation of the Carbonyl Group3.1 Reduction3.2 Knoevenagel Reaction3.3 Addition of Organometallic Compounds3.4 Olefination4 Reactions Involving the Enone Conjugate System С=С–С=О4.1 Reactions with 1,2-Dinucleophiles4.2 Reactions with Compounds Bearing an Active Methylene Group4.3 Reactions with 1,3-Dinucleophiles4.4 Reactions with 1,4-Dinucleophiles5 Functionalization of the Enone Methylene Group C(O)–CH2R5.1 Acylation/Crotonic Condensation and Related Transformations5.2 Enolization6 Functionalization of the Indole Core6.1 [4+2] Cycloaddition6.2 [3+3] Annulation6.3 Electrocyclic Reactions7 Miscellaneous8 Conclusions

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“…Another interesting core is thiazole. Its derivatives have been reported to possess a wide range of biological properties, such as antimicrobial [32][33][34], anticancer [35][36][37], anti-inflammatory [38][39][40], antiviral [41,42], anti-HIV [43,44], antidiabetic [45,46], carbonic anhydrase inhibitory [47][48][49], antitubercular [50,51], and many other [52][53][54] activities. Furthermore, penicillin derivatives [55]; bleomycin [56]; tiazofurin [57], an antineoplastic drug; vitamin B1 [58]; ritonavir, an approved drug for the treatment of HIV [59]; and meloxicam [60] (Figure 3) are also very important thiazole-containing agents approved for human use.…”

Section: Introductionmentioning

confidence: 99%

4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation

Simakov

Карцев²,

Petrou

et al. 2021

Pharmaceuticals

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This manuscript deals with the synthesis and computational and experimental evaluation of the antimicrobial activity of twenty-nine 4-(indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole acylamines. An evaluation of antibacterial activity against Gram (+) and Gram (−) bacteria revealed that the MIC of indole derivatives is in the range of 0.06–1.88 mg/mL, while among fourteen methylindole derivatives, only six were active, with an MIC in the range of of 0.47–1.88 mg/mL. S. aureus appeared to be the most resistant strain, while S. Typhimurium was the most sensitive. Compound 5x was the most promising, with an MIC in the range of 0.06–0.12 mg/mL, followed by 5d and 5m. An evaluation of these three compounds against resistant strains, namely MRSA P. aeruginosa and E. coli, revealed that they were more potent against MRSA than ampicillin. Furthermore, compounds 5m and 5x were superior inhibitors of biofilm formation, compared to ampicillin and streptomycin, in terms Compounds 5d, 5m, and 5x interact with streptomycin in additive manner. The antifungal activity of some compounds exceeded or was equipotent to those of the reference antifungal agents bifonazole and ketoconazole. The most potent antifungal agent was found to be compound 5g. Drug likeness scores of compounds was in a range of −0.63 to 0.29, which is moderate to good. According to docking studies, E. coli MurB inhibition is probably responsible for the antibacterial activity of compounds, whereas CYP51 inhibition was implicated in antifungal activity. Compounds appeared to be non-toxic, according to the cytotoxicity assessment in MRC-5 cells.

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Synthesis, docking, and evaluation of novel thiazoles for potent antidiabetic activity

Cited by 34 publications

References 24 publications

Synthesis, Structure‐Activity Relationship and in silico Studies of Novel Pyrazolothiazole and Thiazolopyridine Derivatives as Prospective Antimicrobial and Anticancer Agents

Synthesis, Structure‐Activity Relationship and in silico Studies of Novel Pyrazolothiazole and Thiazolopyridine Derivatives as Prospective Antimicrobial and Anticancer Agents

Indolylvinyl Ketones: Building Blocks for the Synthesis of Natural Products and Bioactive Compounds

4-(Indol-3-yl)thiazole-2-amines and 4-ιndol-3-yl)thiazole Acylamines as Νovel Antimicrobial Agents: Synthesis, In Silico and In Vitro Evaluation

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