Phenyl Methylidene Research Articles

Synthesis and Biological Screening of Novel Derivatives of Benzothiazol as Anticonvulsant Agents

The Benzothiazole ring system belongs to a much studied class of compound. In the last few decades, the chemistry of benzothiazole and their fused heterocyclic derivatives have received considerable attention owing to their significant and effective biological activity. The present study aimed to design and synthesize novel derivatives of bezothiazole obtained from 3-chloro-4-flouro aniline treated with potassium thiocynide with chloro acetyl chloride gives (7-chloro-6-fluro-1,3-benzothiazol-2-yl) acetyl chloride which is converted into hydrazide and yields the resultant compound derivatives of 2-(7-chloro-6-fluro-1,3-benzothiazol-2-yl) –N’-[(Z)-phenyl methylidene] acetohydrazide (SMVB-IIIA-IIIG).Title compound were synthesized and the structures of newly synthesized compounds were confirmed by IR, Mass and 1H-NMR spectroscopy All the compounds synthesized were confirmed by spectral data and evaluated for their anticonvulsant activity. The Compounds SMVB-IIIC, SMVB-IIIEand SMVB-IIIF showed maximal activity whereas remaining compounds showed good activity.

Design and Synthesis of a Class of Compounds That Inhibit the Growth of Fungi Which Cause Invasive Infections

AbstractInvasive fungal infections are growing causes of morbidity and mortality in immunocompromised patients. However, only one antifungal drug class has been developed in the last 30 years, extremely limiting current therapeutic options. To address unmet medical needs, we performed high‐throughput screening of 9600 chemical compounds and identified an aminohydrazone derivative as a novel and potent antifungal compound. We then designed and synthesized a series of aminohydrazone derivatives, and demonstrated that 1‐[(E)‐[4‐(3′,4′‐dichlorobenxyloxy)phenyl methylidene]amino]‐guanidine had the most potent inhibitory activity and exhibited a broad spectrum of antifungal activities against Candida species (including multidrug resistant C. auris), Aspergillus species, Cryptococcus neoformans, and Rhizopus oryzae. Against C. albicans, the leading cause of Candida infections, the compound had fungicidal activity for planktonic cells at 8 μg mL−1 (25 μM) and anti‐biofilm activity at 34 μg mL−1 (100 μM). This study provides new insights for the development of a new drug class for the treatment of invasive fungal infections which are often refractory to conventional therapies.

ANTI-INFLAMMATORY AND ANTIOXIDANT ACTIVITY OF SYNTHESIZED MANNICH BASE DERIVATIVES OF (2E,6E)-2-[(4-HYDROXY-3-METHOXYPHENYL)METHYLIDENE]-6-(PHENYL METHYLIDENE)CYCLOHEXAN-1-ONE

Objective: To further understand this compound, we synthesized and evaluated the antioxidant and anti-inflammatory activity of a series of itsMannich base derivatives.Methods: We synthesized the compounds via the previously reported Mannich reaction method. Their structures were elucidated by Fouriertransforminfrared,1H-NMR,13C-NMR, and high-resolution mass spectra. The derivatives’ anti-inflammatory and antioxidant activities were testedusing the inhibition of protein denaturation method and the 2,2-diphenyl-2-picrylhydrazyl free radical scavenging assay.Results: The IC50 values for the anti-inflammatory activity of the 2,6-dimethylmorpholine, pyrrolidine, 1-methylpiperazine, and dimethylamineMannich base derivatives 2a–d were 10.67, 10.72, 37.75, and 1.93 μM, respectively; for (2E,6E)-2-({4-hydroxy-3-methoxyphenyl}methylidene)-6-(phenylmethylidene)cyclohexan-1-one (1), diclofenac sodium, and curcumin, the IC50 values were 56.29, 1.52, and 8.43 μM, respectively. The IC50values for the antioxidant activity of compounds 2a–2d were 229.62, 57.29, 280.43, and 219.22 μM, respectively; for compound 1, quercetin, andcurcumin, the IC50 values were 144.22, 27.28, and 26.45 μM, respectively.Conclusion: Substituting Mannich bases into (2E,6E)-2-[(4-hydroxy-3-methoxyphenyl) methylidene]-6-(phenylmethylidene)cyclohexan-1-oneenhanced its anti-inflammatory activity, but lowered its antioxidant activity. Compound 2d, (2E,6E)-2-({3-[(dimethylamino)methyl]-4-hydroxy-5-methoxyphenyl}methylidene)-6-(phenyl methylidene)cyclohexan-1-one, exhibited potent anti-inflammatory activity comparable to diclofenacsodium and four times higher than curcumin. However, further investigation of this compound’s mechanism of action and toxicity is warranted.

An Approach to Computer Aided Drug Design of some Bioactive Cinnamoyl Hydrazones, In Silico and Docking Studies as Possible COX-2 Selective Inhibitors

Recently structural analogue-based drug discovery has become an important tool for designing more potent drugs. This study uses SAR, pharmacophore study and structural analogue-based novel drugs to design selective inhibitor molecules using internet-based tools. Substituted acyl hydrazones are known for wide variety of biological activities, such as analgesic, anti–inflammatory, anti-microbial, anti-convulsant, anti-platelet, anti-tubercular, antiviral, schistomiasis and anti-tumoral activities. In the last decade several cinnamic acid derivatives were reported as potent lipoxygenase inhibitors, antioxidants and anti-inflammatory agents. We found it interesting to combine these particular molecules and design cinnamoyl hydrazones, a series of N-[(1E)-2-substituted phenyl-1-{N'-[(1E)-phenyl methylidene] hydrazine carbonyl} eth-1-en-1-yl] benzamides. The designed compounds were predicted for their drug likeness and oral bioavailability. Selected compounds were docked with COX-2 enzyme and found that they were showing similar interactions as that of SC-558, 1000 time selective standard COX-2 inhibitor.