Antimicrobial screening and one-pot synthesis of 4-(substituted-anilinomethyl)-3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives.

AIM: Synthesis of series of 4-(substituted-anilinomethyl-3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives (4a-4k) and their in vitro antifungal and antibacterial screening. MATERIALS AND METHODS: A series of compounds (4a-4k) was synthesized through direct reductive amination of 3-(naphthalen-2-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde with various substituted aromatic amines using NaBH4 in the presence of I2 as reducing agent. The reaction was carried out in anhydrous methanol under neutral conditions at room temperature. The structures of synthesized compounds (4a-4k) were established on the basis of IR, (1)H and (13)C-NMR, and mass spectral data. RESULTS: All 4-(substituted-anilinomethyl-3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives (4a-4k) were tested in vitro for antifungal and antibacterial activities against different fungal and bacterial strains. Most of the compounds exhibited considerable antifungal activity, but poor antibacterial activity against the test strains. CONCLUSION: In the series compound 4e, 4g, 4j, and 4k, showed excellent antifungal activity against the fungal strain Aspergillus niger (MTCC) 281 and Aspergillus flavus MTCC 277 (% inhibition in the range of 47.7-58.9).

Synthesis and biological evaluation of di- and tri-substituted imidazoles as safer anti-inflammatory-antifungal agents.

PURPOSE: In view of the potential pharmacophoric nature of imidazole nucleus, two series of imidazole derivatives, 2,4-disubstituted-1 H-imidazoles (2a-m) and 1,2,4-trisubstituted-1 H-imidazoles (3a-m), were synthesized with an aim of obtaining dual acting compounds i.e., anti-inflammatory and antifungal agents. MATERIALS AND METHODS: The title compounds were synthesized from 4-methoxyphenyl glyoxal (1) following multistep synthesis, and their structures were established on the basis of modern analytical techniques (IR, NMR and MS). The synthesized imidazoles were tested for their in vivo anti-inflammatory activity. In addition to that, some compounds were also evaluated for their analgesic and ulcerogenic effects. The compounds were also evaluated for their in vitro antifungal activity. RESULTS: Di- and tri-substituted imidazole derivatives (2a-m and 3a-m) were successfully synthesized. In in vivo anti-inflammatory test, six compounds (2 h, 2 l, 3 g, 3 h, 3 l and 3 m) exhibited good anti-inflammatory activity (49.58 to 58.02% inhibition) with minimal GI irritation (severity index; 0.17 to 0.34). These compounds were also tested for their analgesic activity and showed appreciable protection (40.53 to 49.60% protection) against saline-induced writhing test. Indomethacin was used as standard drug for comparison. In antifungal test, two compounds (3 h and 3 l) displayed appreciable antifungal activity (MIC; 12.5 µg mL(-1)) against the fungal strains tested. CONCLUSION: Two compounds, 2-(4-nitrophenyl)-4-(4-methoxyphenyl)-1-phenyl-1H-imidazole (3 h) and 2,4-di-(4-methoxyphenyl)-1-phenyl-1H-imidazole (3 l), emerged as lead compounds having dual biological activities; good anti-inflammatory as well as antifungal effect with lesser GI irritation.

Advances in synthetic approach to and antifungal activity of triazoles.

Several five membered ring systems, e.g., triazole, oxadiazole dithiazole and thiadiazole with three heteroatoms at symmetrical or asymmetrical positions have been studied because of their interesting pharmacological properties. In this article our emphasis is on synthetic development and pharmacological activity of the triazole moiety which exhibit a broad spectrum of pharmacological activity such as antifungal, antibacterial, anti-inflammatory and anticancer etc. Triazoles have increased our ability to treat many fungal infections, for example, candidiasis, cryptococcal meningitis, aspergillosis etc. However, mortality due to these infections even with antifungal therapy is still unacceptably high. Therefore, the development of new antifungal agents targeting specific fungal structures or functions is being actively pursued. Rapid developments in molecular mycology have led to a concentrated search for more target antifungals. Although we are entering a new era of antifungal therapy in which we will continue to be challenged by systemic fungal diseases, the options for treatment will have greatly expanded.

Synthesis of cyanopyridine and pyrimidine analogues as new anti-inflammatory and antimicrobial agents.

A new series of substituted benzylidene acetophenone (Ia-Ih), 2-amino-4, 6- substituted diphenylpyridine-3-carbonitrile (IIa-IIh) and 4, 6-substituted diphenylpyrimidin-2-amine (IIId-IIIg) were synthesized and evaluated for anti-inflammatory and antimicrobial activities. Four compounds (Ie, If, IIh and IIId) have shown good anti-inflammatory activity when compared to standard drug indomethacin. Two compound (Ie and IIh) displayed significant activity against gram -ve bacteria (E. Coli) and three compounds (IId, IIf and IIIh) displayed good activity against gram +ve bacteria (S. aureus) on comparison with the standard drug ofloxacin.

Synthesis and biological evaluation of some new pyridazinone derivatives.

A series of pyridazinone derivatives (19-34) were synthesized with an aim to synthesize safer anti-inflammatory agents. The compounds were evaluated for their anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation (LPO) actions. The percentage inhibition in edema at different time intervals indicated that compounds 20, 26, 28 and 34 exhibited good anti-inflammatory potential, comparable with that of ibuprofen (85.77%) within a range of 67.48-77.23%. The results illustrate that 5-(4-fluoro-benzyl)-3-(4-chloro-phenyl)-1,6-dihydro-6-pyridazinone (26) and 5-(4-chloro-benzyl)-3-(4-chloro-phenyl)-1,6-dihydro-6-pyridazinone (20) showed best anti-inflammatory activity. Furthermore, activity is more in case of chloro substitution as compared with methyl-substitution. The compounds synthesized were also evaluated for their ulcerogenic and LPO action and showed superior gastrointestinal safety profile along with reduction in LPO as compared with that of the ibuprofen.

Synthesis, antidepressant and antifungal evaluation of novel 2-chloro-8-methylquinoline amine derivatives.

A new series of N-[(2-chloro-8-methylquinolin-3-yl)methyl]-(substituted)-aniline/butylamine/cyclohexylamine/benzylamine derivatives (4a-p) was synthesized by nucleophilic substitution reaction of 2-chloro-3-(chloromethyl)-8-methylquinoline 3 with various aliphatic and aromatic amines in absolute ethanol in the presence of triethylamine (TEA). The newly synthesized secondary amines were characterized by the combined use of IR, 1H NMR, 13C NMR, mass spectral data and microanalyses. The antidepressant activity of the synthesized compounds (4a-p) was evaluated by Forced swim test in rats and their neurotoxicity was evaluated by the rotarod test. Test compounds and clomipramine were administered intraperitoneally at dose of 100 mg/kg and 20 mg/kg respectively. Preliminary antidepressant screening of compounds (4a-p) revealed that compounds 4b, 4c, 4d, 4e, 4i and 4o significantly (P<0.01) reduces the duration of immobility time. These compounds were also tested in-vitro for MAO inhibitory effect. All the compounds were also screened for antifungal activity against Aspergillus niger MTCC 281, Aspergillus flavus MTCC 277, Monascus purpureus MTCC 369 and Penicillium citrinum NCIM 768 strains.

Antimicrobial investigation of Linum usitatissimum for the treatment of acne.

Light petroleum, dichloromethane and methanolic extracts of Linum usitatissimum were investigated using GC/MS. The main components of three sequential extracts were methyl linolenate (11.9-33.9%) and methyl linoleate (3.4-9.1%). Components possessing antimicrobial activity against acne causing bacteria, namely alpha-linolenic acid (7.0 -7.1%), alpha-terpinene (1.7-3.1%), terpinen-4-ol (1.3-4.6%), 4-cymene (1.6-7.1%) and alpha-pinene (1.1%), were found in varying amounts. Antimicrobial screening indicated that the light petroleum extract was more active against aerobic and anaerobic test strains with a MIC value of 1.25 mg/mL and a MBC of 2.5 mg/mL against S. aureus and P. acnes. A MIC of 2.5 mg/mL was observed against S. epidermidis.

Emerging trends in contract research industry in India.

A Contract Research Organization (CRO) is a service organization that provides support to the pharmaceutical industry and offers a wide range of "outsourced" pharmaceutical research services to aid in R&D process and is thus an essential tool for undertaking clinical trials in the present scenario when high stakes are involved in the drug discovery process. This industry also offers a safe option of investment as the industry is largely recession-proof, with a significant upscale growth. Presently India occupies a very small pie of the global market share in the Clinical Trials Industry but it is estimated to conduct nearly 5% of global clinical trials by 2012. The global CRO industry valued $18 bn in 2008 and the market is expected to grow at an annual rate of 14% between 2009 and 13. Top multinational pharmaceuticals companies are venturing into the Indian business, in collaboration with the Indian Drug Companies. According to a recent study by Mckinsey & Company, the Indian Clinical Research Industry can attract $1.5 bn of revenue from US and EU by 2010. Such an increase in outsourcing from the western countries has led the global pharma companies and Indian entrepreneurs to set up Contract Research Organizations (CROs) in India. To bring this into realization and fulfil the market demand, while simultaneously aiding in improving the country's economical standards and market position, joint and well-coordinated efforts on part of the government, industry, and working professionals are needed in terms of regulatory affairs, audits, transparency in work affairs, garnering patient confidence, and pharmacovigilance.

Structural modifications of quinoline-based antimalarial agents: Recent developments.

Antimalarial drugs constitute a major part of antiprotozoal drugs and have been in practice for a long time. Antimalarial agents generally belong to the class of quinoline which acts by interfering with heme metabolism. The recent increase in development of chloroquine-resistant strains of Plasmodium falciparum and failure of vaccination program against malaria have fuelled the drug discovery program against this old and widespread disease. Quinoline and its related derivative comprise a class of heterocycles, which has been exploited immensely than any other nucleus for the development of potent antimalarial agents. Various chemical modifications of quinoline have been attempted to achieve analogs with potent antimalarial properties against sensitive as well as resistant strains of Plasmodium sp., together with minimal potential undesirable side effects. This review outlines essentially some of the recent chemical modifications undertaken for the development of potent antimalarial agents based on quinoline.

Synthesis and biological screening of di- and trisubstituted imidazoles.

Disubstituted imidazoles were prepared by reacting appropriate phenylglyoxal with different aryl aldehydes in the presence of ammonium acetate. Trisubstituted imidazoles were prepared by reacting disubstituted imidazoles with chlorobenzene in the presence of catalytic amount of triethylamine (TEA). The synthesized compounds were characterized on the basis of IR, 1H-NMR and mass spectral data and elemental analysis results. They were tested for their antiinflammatory and antimicrobial actions. Two compounds showed good antiinflammatory activity in carrageenan induced rat paw edema test with very low ulcerogenic activity. Fair number of compounds were found to have significant antimicrobial activity especially against fungal species.

Biological activities of pyrazoline derivatives--a recent development.

Pyrazolines are well known and important nitrogen containing 5-membered heterocyclic compounds and various methods have been worked out for their synthesis. Numerous pyrazoline derivatives have been found to possess considerable biological activities, which stimulated the research activity in this field. They have several prominent effects, such as antimicrobial, antimycobacterial, antifungal, antiamoebic, anti-inflammatory, analgesic, antidepressant and anticancer activities. They also possess some potent receptor selective biological activity like Nitric oxide synthase (NOS) inhibitor and Cannabinoid CB1 receptor antagonists activity. 4,5-dihydro-1H- pyrazolines seem to be the most frequently studied pyrazoline type compounds. As a result, a large number of such pyrazolines using different synthetic methods for their preparation have been described in the chemistry literature. The present review provides an insight view to pyrazolines synthesis and its biological activities along with the compilation of recent patents on pyrazolines.