Neelam Jain

Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea

Several new 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea were synthesized and screened for anticonvulsant, CNS depressant and sedative-hypnotic activity in the mice. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight synthesized compounds were examined in the maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Spectroscopic data and elemental analysis were consistent with the newly synthesized compounds. The neurotoxicity was assessed using the rotorod method. Compounds E1, E6, E9, E12, P3, P4 and P6 were found to be active in the MES screen whereas E1, P4, P6 and P11 were found to be active in the scPTZ screen. All except E6, E11 and P6 showed more than 50% decrease in locomotor activity at 1h of compound administration via actophotometer screen. CNS depressant activity screened with the help of the forced swim method resulted into some potent compounds. All the compounds were found to exhibit potent CNS depressants activity as indicated by increased immobility time. It can be concluded that newly synthesized compounds possessed promising CNS activities.

Estrogenic and Anti-Alzheimer’s studies of Zingiber officinalis as well as Amomum subulatum Roxb.: the success story of dry techniques

The extracts of ginger and cardamom were chosen for studies on estrogen receptors and Alzheimer’s disease on the basis of various in silico studies of their constituents. Estrogenic effect was evaluated by uterine weight method while effect on learning and memory was studied using elevated plus maze method. Cardamom extract showed better estrogenic effect as compared to ginger. Reverse trend was observed in case of anti-alzheimer’s activity. Both extracts exhibited considerable improvement in learning and memory.

3-Aryl-1-phenyl-1H-pyrazole derivatives as new multitarget directed ligands for the treatment of Alzheimer's disease, with acetylcholinesterase and monoamine oxidase inhibitory properties

A series of 3-aryl-1-phenyl-1H-pyrazole derivatives was synthesized in good yield and assayed in vitro as inhibitors of the mice acetylcholinesterase (AChE) and two goat liver monoamine oxidase (MAO) isoforms, MAO-A and MAO-B. Most of the compounds demonstrated a good AChE and selective MAO-B inhibitory activities in the nanomolar or low micromolar range. N-((3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-yl) methylene) benzenamine (3e, pIC50 = 4.2) and N-((4-fluorophenyl)-1-phenyl-1H-pyrazole-4-yl) methylene) methanamine (3f, pIC50 = 3.47) were the most potent AChE and highly selective MAO-B inhibitors respectively. Structure activity relationships showed that chloro derivatives were more effective AChE inhibitors as compared to fluoro derivatives while reverse trend was observed in MAO-B inhibitory activity. With the aid of modeling studies, potential binding orientations as well as interactions of the compounds in the AChE and MAO-B active sites were examined.

Synthesis and antimalarial potential of some novel quinoline-pyrazolopyridine derivatives

A series of 1-(4-methylquinolin-2-yl)-4,6-diaryl-1H-pyrazolo[3,4-b]pyridin-3-amine derivatives was synthesized by the reaction of 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-ones with 2-chloro-4,6-diphenylnicotinonitrile analogues in the presence of 2-hydrazino-4-methyl quinoline and ethanol. The newly synthesized compounds were characterized by IR, 1H NMR and mass spectral data. The synthetic series of novel quinoline-pyrazolopyridine hybrids were screened for in vitro schizont maturation assay against chloroquine sensitive 3D7 strain of Plasmodium falciparum, from which the most five active analogues were further evaluated for in vivo 4-day suppressive test in Swiss albino mice. Among the series, 5p (containing 4-Cl substituent attached to both aryl ring) portrayed considerable potent antimalarial activity during in vitro as well as in vivo study.

Synthesis, Characterization and Molecular Docking Studies of Novel N-(benzimidazol-1-ylmethyl)-4-chlorobenzamide Analogues for Potential Anti-inflammatory and Antimicrobial Activity

BACKGROUND The benzimidazole ring is an important pharmacophore in modern drug discovery. Mannich reaction is one of the versatile reaction widely used in organic synthesis. Mannich base derivatives play an important role in medical field with diverse biological actions. OBJECTIVE A series of N-(benzimidazol-1-ylmethyl)-4-chlorobenzamide derivatives (3a- 3m) were synthesized and evaluated for anti-inflammatory and antimicrobial potential. METHOD Mannich reaction was used to synthesize N-(benzimidazol-1-ylmethyl)-4- chlorobenzamide analogues. The structures of novel target compounds were elucidated by spectral and analytical techniques and screened for in vivo anti-inflammatory activity and ulcerogenic activity. In addition, the prepared derivatives were also evaluated for in vitro antimicrobial activity against gram negative, gram positive and fungal strains. Further, in silico studies were carried out to define the interaction of the title compounds with COX-2 enzyme and microbial protein. RESULTS The results revealed that out of thirteen molecules, compound 3a (containing chloromethyl substituent at 2-position of benzimidazole) showed significant antiinflammatory effect at a dose of 100 mg/kg p.o. and the experimental data was statistically significant at p≤0.05 level. Diclofenac sodium was taken as standard drug for antiinflammatory activity. Furthermore, derivative 3e (containing 2-chlorophenyl moiety at 2- position of benzimidazole scaffold) was found to be the most effective antimicrobial compound among the synthesized derivatives. Ciprofloxacin and clotrimazole were used as reference antimicrobial agents. Results from in vivo and in vitro studies of synthesized analogues were found to be in good correlation with in silico study. CONCLUSION These results designate that N-(Benzimidazol-1-ylmethyl)-4-chlorobenzamide analogues, substituted with halogen functionality, could be used as potential lead for designing more potent anti-inflammatory and antimicrobial agents.

A synthetic approach and molecular docking study of hybrids of quinazolin-4-ones and thiazolidin-4-ones as anticancer agents

A series of 3-(4-(2-(aryl)-4-oxothiazolidin-3-yl)phenyl-2-phenylquinazolin-4(3H)-one derivatives were synthesized in appreciable yield by using anthranilic acid as a starting material. The structures of synthesized compounds (QT1–QT10) were confirmed on the basis of various spectral techniques and analytical methods. These synthesized compounds were screened for their in vitro antitumor activity against the human breast cancer cell line (MCF-7), human hepatocellular cancer cell line (HepG2) using MTT assay method and doxorubicin as a standard drug. Compound 3-(4-(2-(3-chlorophenyl)-4-oxothiazolidin-3-yl)phenyl-2-phenylquinazolin-4(3H)-one (QT4) showed comparable cytotoxic activity against Hep-G2 cell line. Compound 3-(4-(2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)phenyl-2-phenylquinazolin-4(3H)-one (QT5) showed comparable cytotoxic activity against MCF-7 cell line while QT6, QT7, QT8 were the less cytotoxic as they showed high IC50 and away from that of doxorubicin. The remaining compounds did not show significant activity against both the cell lines. To understand the interaction of series with active binding site of receptor, docking study was performed with topoisomerase-II co-crystallized with adenylyl-imidodiphosphate complex using AutoDockVina. There was a good correlation between in vitro and in silico study. Thus, this investigation leads to the identification of newer anticancer agents.