Synthesis and spectral properties of some N-substituted derivatives of phenol blue

Bioorganic & Medicinal Chemistry

et al. 2013

Cyclooxygenase-2 (COX-2) and 5-Lipoxygenase (5-LOX) enzyme have been found to play a role in promoting growth in colon cancer cell lines. The di-tert-butyl phenol class of compounds has been found to inhibit both COX-2 and 5-LOX enzymes with proven effectiveness in arresting tumor growth. In the present study, the structural analogs of 2, 6 di-tert-butyl-p-benzoquinone (BQ) appended with hydrazide side chain were found to inhibit COX-2 and 5-LOX enzymes at micromolar concentrations. Molecular docking of the compounds into COX-2 and 5-LOX protein cavities indicated strong binding interactions supporting the observed cytototoxicities. The signaling interaction between endogenous hyaluronan and CD44 has been shown to regulate COX-2 activities through ErbB2 receptor tyrosine kinase (RTK) activation. In the present studies it has been observed for the first time, that three of our COX/5-LOX dual inhibitors inhibit proliferation upon hydrazide substitution and prevent the activity of pro-angiogenic factors in HCA-7, HT-29, Apc10.1 cells as well as the hyaluronan synthase-2 (Has2) enzyme over-expressed in colon cancer cells, through inhibition of the Hyaluronan/CD44v6 cell survival pathway. Since there is a substantial enhancement in the antiproliferative activities of these compounds upon hydrazide substitution, the present work opens up new opportunities for evolving novel active compounds of BQ series for inhibiting colon cancer.

Section: Resultsmentioning

confidence: 99%

Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan–CD44v6 pathway and inducing cytotoxicity in colon cancer cells

Misra

Ghatak

Bioorganic & Medicinal Chemistry

et al. 2013

“…The signals at 12.38, 12.14 and 11.65 ppm are attributed to the D 2 O‐exchangeable N2H, N1H and O3H protons, respectively. The two singlets at 1.25 and 1.38 ppm correspond to two sets of magnetically non‐equivalent tert ‐butyl groups . The singlet at 8.56 ppm is assigned to the azomethine proton (C15H), which confirms the formation of hydrazone.…”

Section: Resultsmentioning

confidence: 88%

Mononuclear Co(III), Ni(II) and Cu(II) complexes of tridentate di‐tert‐butylphenylhydrazone: Synthesis, characterization, X‐ray crystal structures, Hirshfeld surface analysis, molecular docking and in vivo anti‐inflammatory activity

Chimmalagi

Kendur

et al. 2018

Applied Organom Chemis

A new hydrazone (LH 2 ) derived from the condensation of 2-(4-fluorobenzamido) benzohydrazide with 3,5-di-tert-butyl-2-hydroxybenzaldehyde was used to synthesize Co(III), Ni(II) and Cu(II) complexes. These were characterized using various physicochemical, thermal, spectroscopic and single-crystal X-ray diffraction techniques. All the complexes crystallize in a monoclinic crystal system with P2 1 /n space group and Z = 4. Structural studies of [Co(L)(LH)]⋅H 2 O indicate the presence of both amido and imidol tautomeric forms of the ligand, resulting in a distorted octahedral geometry around the Co(III) ion. On the other hand, in the [Ni(L)(DMF)] and [Cu(L)(H 2 O)] complexes, the ligand coordinates to the metal through imidol form resulting in distorted square planar geometry, in which the fourth position is occupied by the oxygen of coordinated DMF in [Ni(L)(DMF)] and by a water molecule in [Cu(L)(H 2 O)]. Hirshfeld surface calculations were performed to explore hydrogen bonding and C-H⋅⋅⋅π interactions.Molecular docking studies were carried out to study the interaction between the synthesized compounds and proteins (cyclooxygenase-2 and 5-lipoxygenase). The complexes along with the parent ligand were screened for their in vivo anti-inflammatory activity, using the carrageenan-induced rat paw oedema method. The complexes show significant anti-inflammatory potencies.

“…This signal is being shifted to 8.69 ppm due to the participation of azomethine nitrogen in coordination. The two sharp singlets in LH 3 / 5 at 1.28/0.90 and 1.39/1.21 ppm correspond to two sets of magnetically non‐equivalent tert‐ butyl groups . The signals corresponding to the protons of aromatic moieties of LH 3 and 5 were observed in the range of 7.2–8.25 and 6.73–8.18 ppm, respectively.…”

Section: Resultsmentioning

confidence: 99%

Mononuclear Co(III), Ni(II) and Cu(II) complexes of 2‐(2,4‐dichlorobenzamido)‐N'‐(3,5‐di‐tert‐butyl‐2‐hydroxybenzylidene)benzohydrazide: Structural insight and biological assay

Chimmalagi

Kendur

et al. 2018

Applied Organom Chemis

A series of mononuclear metal complexes of Co(III), Ni(II) and Cu(II) with 2-(2,4-dichlorobenzamido)-N′-(3,5-di-tert-butyl-2-hydroxybenzylidene)benzohydrazide (LH 3 ) have been synthesized and characterized using various physico-chemical, spectroscopic and single crystal X-ray diffraction techniques. Structural studies of [Co(LH)(LH 2 )]·H 2 O (4) revealed the presence of both amido and imidol tautomeric forms of LH 3 , resulting in a distorted octahedral geometry around the Co(III) ion. [Ni(LH)(H 2 O)]·H 2 O (5) and [Cu(LH)(H 2 O)]·H 2 O (6) are isomorphous structures and crystallize in the monoclinic P2 1 /c space group. The crystal structures of 4, 5 and 6 are stabilized by hydrogen bonds formed by the enclathrated water molecules, C-H···π and π···π interactions. Complexes along with the ligand (LH 3 ) were screened for their in vivo anti-inflammatory activity (carrageenan-induced rat paw edema method) and in vitro antioxidant activity (DPPH free radical scavenging assay). Metal complexes have shown significant anti-inflammatory and antioxidant potential.KEYWORDS anti-inflammatory activity, antioxidant activity, crystal structure, di-tert-butyl phenylhydrazone, isomorphous metal complexes