Hanmant K. Gaikwad

Synthesis and anti-inflammatory activity of some novel 3-phenyl-N-[3-(4-phenylpiperazin-1yl)propyl]-1H-pyrazole-5-carboxamide derivatives.

A new series of 3-phenyl-N-[3-(4-phenylpiperazin-1yl)propyl]-1H-pyrazole-5-carboxamide derivatives were synthesized and investigated their anti-inflammatory activities using carrageenan-induced rat paw edema model in vivo. All the synthesized compounds were found to be potent anti-inflammatory agents.

Chemoenzymatic synthesis with lipase catalyzed resolution and evaluation of antitumor activity of (R/S)-2-[2-hydroxy-3-(4-phenylpiperazin-1-yl)propyl]-1H-pyrrolo[3,4-b]quinolin-3(2H)-one

Synthesis, characterization, resolution and evaluation of novel (R/S)-2-[2-hydroxy-3-(4-phenylpiperazin-1-yl)propyl]-1H-pyrrolo[3,4-b]quinolin-3(2H)-one derivatives are described. Enantiomerically pure compounds were isolated in good to excellent yield with high enantiomeric excess under mild reaction conditions by using Candida antarctica B (CAL-B) and Candida rugosa (CRL) Lipases. Newly synthesized and resolved compounds were screened for their antitumor activity against cancer cells such as human neuroblastoma SK-N-SH and human lung carcinoma A549 cell line in vitro. The results have shown that the compound 1 S-(-) alcohol was more effective in inhibiting the tumor cell growth.

Convenient Approach for the One-Pot, Three-Component Synthesis of Triheterocyclic 4H-Pyrimido[2,1-b]benzothiazole Derivatives Using TBAHS

Abstract An efficient and convenient synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives has been achieved by a one-pot, three-component condensation reaction of 2-aminobenzothiazole (1) with substituted benzaldehydes (2a–f) and β-dicarbonyl derivatives (3a–e) in presence of 30 mol% of tetrabutylammonium hydrogen sulfate (TBAHS) in good to excellent yields. GRAPHICAL ABSTRACT

Design and synthesis of 3-(3-((9H-carbazol-4-yl)oxy)-2-hydroxypropyl)-2-phenylquinazolin-4(3H)-one derivatives to induce ACE inhibitory activity.

In an attempt to develop a new class of cardiovascular drugs, a series of novel carbazolyloxy phenylquinazoline derivatives 9a-g have been synthesized and evaluated as angiotensin converting enzyme (ACE) inhibitors. Most of these compounds exhibited activity as significant ACE inhibitors and three compounds (9b, 9c & 9e) showed maximum inhibitory potency in enzyme based assays. To render support to the experimental results, a series of quinazolinone derivatives were docked into active site of ACE and identified the probable binding modes compared to Lisinopril. Also we have identified common pharmacophore hypothesis (AAADDRR) among the best docked conformers of most potent compounds in a series of compounds. The most potent 9b, 9c, 9e compounds shared common active site with the Lisinopril binding site and retained the key active site residue interactions. The obtained results from pharmacological and molecular modeling studies can be utilized for further optimization of identified hits for selective inhibition of ACE.

Luotonin-A based quinazolinones cause apoptosis and senescence via HDAC inhibition and activation of tumor suppressor proteins in HeLa cells.

A series of novel quinazolinone hybrids were synthesized by employing click chemistry and evaluated for anti-proliferative activities against MCF-7, HeLa and K562 cell lines. Among these cell lines, HeLa cells were found to respond effectively to these quinazolinone hybrids with IC50 values ranging from 5.94 to 16.45 μM. Some of the hybrids (4q, 4r, 4e, 4k, 4t, 4w) with promising anti-cancer activity were further investigated for their effects on the cell cycle distribution. FACS analysis revealed the G1 cell cycle arrest nature of these hybrids. Further to assess the senescence inducing ability of these compounds, a senescence associated β-gal assay was performed. The senescence inducing nature of these compounds was supported by the effect of hybrid (4q) on p16 promoter activity, the marker for senescence. Moreover, cells treated with most effective compound (4q) show up-regulation of p53, p21 and down-regulation of HDAC-1, HDAC-2, HDAC-5 and EZH2 mRNA levels. Docking results suggest that, the triazole nitrogen showed Zn(+2) mediated interactions with the histidine residue of HDACs.

Electrospray ionization tandem mass spectrometry of 3-phenyl-N-(3-(4-phenylpiperazin-1-yl)propyl)-1H-pyrazole-5-carboxamide derivatives: unusual fragmentation involving loss of 11 u.

Many pharmaceuticals are synthetic compounds, and a large number of them are heterocycles. Common examples are the widely used arylpyrazoles in medicinal and pesticide chemistry. Several of the pyrazole derivatives are known to exhibit a wide range of biological activities such as anti-hyperglycemic, analgesic, anti-inflammatory, anti-pyretic, anti-bacterial, hypoglycemic, sedative–hypnotic activity and anticoagulant activity. Recently, some arylpyrazoles were reported to have non-nucleoside HIV-1 reverse transcriptase inhibitory activity. They may prove to be clinically useful compounds and extensive studies have been devoted to arylpyrazole derivatives such as Celecoxib, a well-known COX-2 inhibitor. As a part of an ongoing synthetic research program towards the synthesis of novel and alternative non-steroidal antiinflammatory drugs, we have synthesized a new series of 3-phenyl-N-[3-(4-phenylpiperazin-1-yl)propyl]-1H-pyrazole-5carboxamide derivatives and evaluated their anti-inflammatory activity to inhibit carrageenan-induced paw edema in rats. An initial examination of the electrospray ionization (ESI) mass spectra of these compounds revealed an interesting and unusual apparently impossible fragmentation involving loss of 11 u. As there exist no reports in the literature on mass spectrometric studies of the title compounds and also because of the observed unusual fragmentation, we have undertaken a detailed study of these compounds using ESI tandemmass spectrometry (MS/MS) in combinationwith accuratemassmeasurements and density functional theory (DFT) calculations. ESI mass spectra of 3-phenyl-1H-pyrazole-5-carboxamide derivatives (Scheme 1) were recorded using a LCQ ion trap mass spectrometer (Thermo Finnigan, San Jose, CA, USA), equipped with an ESI source. The data acquisition was under the control of Xcalibur software (Thermo Finnigan). The typical source conditions were: spray voltage, 5 kV; capillary voltage, 15–20 V; heated capillary temperature, 200 C; tube lens offset voltage, 20 V; sheath gas (N2) pressure, 30 psi; and helium was used as damping gas. For the ion trap mass analyzer, the automatic gain control (AGC) settings were 2 10 counts for a full-scanmass spectrum and 2 10counts for a full product ion mass spectrum with a maximum ion injection time of 200 ms. In the full-scan MS and MS modes, the precursor ion of interest was first isolated by applying an appropriate waveform across the end-cap electrodes of the ion trap to resonantly eject all trapped ions, except those ions of the m/z ratio of interest. The isolated ions were then subjected to a supplementary ac signal to resonantly excite them and to induce the collision-activated dissociation (CAD) process. The collision energies used were 20–35 eV. The excitation time used was 30 ms and isolation width used was 1.0 Da.