Hybrid molecules: The privileged scaffolds for various pharmaceuticals

Shaveta,; Mishra, Sahil; Singh, Palwinder

doi:10.1016/j.ejmech.2016.08.039

Cited by 394 publications

(120 citation statements)

References 143 publications

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“…In this study, we employed one of the classical medicinal chemists’ tools—the combination of two pharmacophores in one molecule . The concept of hybrid drugs is also a valuable strategy to overcome the limitations of a combined therapy, as the resulting molecules could exhibit inhibitory activities on multiple targets .…”

Section: Introductionmentioning

confidence: 99%

“…[49,50] In this study,w ee mployed one of the classical medicinal chemists' tools-the combination of two pharmacophores in one molecule. [7,[51][52][53][54] The concept of hybridd rugs is also av aluable strategy to overcome the limitations of ac ombined therapy,a st he resulting molecules could exhibit inhibitory activities on multiple targets. [55] The hybridc ompounds described here, SAHAquines, combine motifs of SAHA, an anticancer agent with weak antiplasmodial activity,a nd PQ, an antimalarial drug with low antiproliferative activity.…”

Section: Introductionmentioning

confidence: 99%

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SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

et al. 2018

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We report the synthesis of SAHAquines and related primaquine (PQ) derivatives. SAHAquines are novel hybrid compounds that combine moieties of suberoylanilide hydroxamic acid (SAHA), an anticancer agent with weak antiplasmodial activity, and PQ, an antimalarial drug with low antiproliferative activity. The preparation of SAHAquines is simple, cheap, and high yielding. It includes the following steps: coupling reaction between primaquine and a dicarboxylic acid monoester, hydrolysis, a new coupling reaction with O‐protected hydroxylamine, and deprotection. SAHAquines 5 a–d showed significant reduction in cell viability. Among the three human cancer cell lines (U2OS, HepG2, and MCF‐7), the most responsive were the MCF‐7 cells. The antibodies against acetylated histone H3K9/H3K14 in MCF‐7 cells revealed a significant enhancement following treatment with N‐hydroxy‐N′‐{4‐[(6‐methoxyquinolin‐8‐yl)amino]pentyl}pentanediamide (5 b). Ethyl (2E)‐3‐({4‐[(6‐methoxyquinolin‐8‐yl)amino]pentyl}carbamoyl)prop‐2‐enoate (2 b) and SAHAquines were the most active compounds against both the hepatic and erythrocytic stages of Plasmodium parasites, some of them at sub‐micromolar concentrations. The results of our research suggest that SAHAquines are promising leads for new anticancer and antimalarial agents.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

et al. 2018

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“…Hence, derivatization of 2 may allow better drugs with less toxic profile. Recently, molecular hybridization concept, which offers the combining of two pharmacophores usually through a linker into a single chemical entity, has received increasing interest in the quest of new drug discovery . Inspired by this perception, we intended that amalgamation of 2 with 1 using amino acids as linkers may offer synergistic anti‐inflammatory effect.…”

Section: Introductionmentioning

confidence: 99%

Novel Hybrid Molecules of Epinastine and Mefenamic Acid for Bioactive Assessment as Potential Anti‐inflammatory Agents

Lee

Damodar

Lee

et al. 2020

Bulletin Korean Chem Soc

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A set of novel epinastine (1) and mefenamic acid (2) hybrids (3-7) tethered via amide bond were designed and synthesized with the artistry of molecular hybridization. Then their inhibitory effect on nitric oxide (NO) production in LPS-induced RAW-264.7 macrophages and the expression levels of prostaglandin (PG) synthesis regulatory genes were evaluated in vitro. All the hybrids were found to have remarkable NO production inhibitory potential with IC 50 values ranging in between 27.69 AE 3.06 and 40.19 AE 5.52 μM without notable cytotoxicity (CC 50 ≥ 100 μM) except 6. Comparing the inhibitory effects, cytotoxicity and in vitro efficacy index (iEI), 4 (IC 50 = 32.09 AE 4.04 μM; iEI = 6.23) and 7 (IC 50 = 27.69 AE 3.06 μM; iEI = 6.40) were better suited than other hybrids as well as their parent compounds EH and MA. This outcome was further harmonized with the reduced microsomal prostaglandin E synthase-1 expression and unaltered housekeeping COX-1 expression by hybrids 4 and 7 treatment. Altogether, our findings signify that hybrids 4 and 7 may serve as platforms for continued investigations for the development of more efficient anti-inflammatory agents.

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“…Isatin derivatives containing benzyl substituent at endocyclic nitrogen are of special interest to date. They are shown to act as caspases‐3 and ‐7 inhibitors, antitubercular, [ ][ ] antileukemia and antimicrobial agents [ ][ ] ( Figure ). The analysis of works on design and target synthesis of biologically active isatin‐3‐acylhydrazones showed a strong dependence of the type and level of activity on the structure of the functional substituent in the hydrazone fragment .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Antimicrobial Study of Novel 1‐Benzylated Water‐Soluble Isatin‐3‐hydrazones

Богданов

Zaripova

Voloshina

et al. 2018

Chemistry & Biodiversity

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A high-yield synthesis of some novel isatin-3-acylhydrazones on the base of 5-ethylisatin derivatives and Girard's reagent T is described. Antimicrobial activity preliminary SAR study of both 1-benzylated isatins and water-soluble hydrazones was established. The most active against Staphylococcus aureus and Bacillus cereus are ammonium salts bearing 3,4-dichloro- or 4-CF substituents in benzyl fragment.

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Hybrid molecules: The privileged scaffolds for various pharmaceuticals

Cited by 394 publications

References 143 publications

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents

Novel Hybrid Molecules of Epinastine and Mefenamic Acid for Bioactive Assessment as Potential Anti‐inflammatory Agents

Synthesis and Antimicrobial Study of Novel 1‐Benzylated Water‐Soluble Isatin‐3‐hydrazones

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