Rajesh A. Rane

Synthesis and evaluation of novel 4-nitropyrrole-based 1,3,4-oxadiazole derivatives as antimicrobial and anti-tubercular agents

We report synthesis and antimicrobial evaluation of 42 novel 4-nitropyrrole-based 1,3,4-oxadiazoles. The synthesized molecules were evaluated for anti-bacterial, anti-fungal and anti-tubercular activities. Promisingly, most of the compounds showed equal or more potency than standard ciprofloxacin against Staphylococcus aureus, Bacillus subtilis and Escherichia coli. Compound 5e exhibited highest anti-tubercular activity (0.46 μg/mL) close to that of standard Isoniazid (0.40 μg/mL). Equal antifungal activity (1.56 μg/mL) compared to standard Amphotericin-B was shown by most of the compounds. All the N-methylated compounds showed more potent to equal activity against MSSA (MIC 0.39-1.56 μg/mL) and MRSA (MIC 0.78-1.56 μg/mL). All compounds were tested for mammalian cell toxicity using VERO cell line and were found to be non-toxic.

Synthesis and evaluation of novel 1,3,4-oxadiazole derivatives of marine bromopyrrole alkaloids as antimicrobial agent

In an attempt to identify new potential lead as antimicrobial agent, twenty hybrids of marine bromopyrrole alkaloids with 1,3,4-oxadiazole were designed based on molecular hybridization technique and synthesized. Synthesized molecules were evaluated for their antibacterial, antifungal and antitubercular activities. Hybrids 5d, 5i, 5j and 5k exhibited equivalent antibacterial activity (MIC of 1.56 μg/mL) compared with standard drug ciprofloxacin against Staphylococcus aureus and Escherichia coli. Equal antifungal activity (MIC of 1.56 μg/mL) was shown by of hybrids 5j, 5k and 7d compared with standard Amphotericin-B. The inhibition of Mycobacterium tuberculosis at concentrations as low as 1.6 and 1.5 μg/mL by compounds 5f and 7d respectively indicates that these compounds can act as leads for development of newer anti-TB compounds.

Synthesis and evaluation of novel chloropyrrole molecules designed by molecular hybridization of common pharmacophores as potential antimicrobial agents

In an attempt to identify new potential lead as antimicrobial agent, 31 novel chloropyrrole derivatives of aroyl hydrazones and chalcones incorporating common pharmacophore of pyoluteorin derivatives were synthesized. Antimicrobial activity of the synthesized compounds was evaluated using broth dilution technique. Based on biological evaluation data it was observed that activity increases as the number of chlorines on pyrrole core increases. Few 1H-pyrrole-2-carbohydrazide derivatives shows activity equivalent to the standard drug ciprofloxacin. Thus, these compounds can act as potential lead for further antibacterial studies.

Synthesis and antibiofilm activity of marine natural product-based 4-thiazolidinones derivatives.

4-Thiazolidinones derivatives of marine bromopyrrole alkaloids were synthesized as potential antibiofilm compounds. Among the synthesized compounds, some showed promising antibiofilm activity. Biological data revealed that 1,3-thiazolidin-4-one derivatives are more potent antibiofilm agents compared to 1,3-thiazinan-4-ones. Antibiofilm activity of compound 4b, 4c (MIC=0.78 μg/ml) was 3-fold superior than standard vancomycin (MIC=3.125 μg/ml) while activity of compound 4d, 4f, 4g and 4h was 2-fold (MIC=1.56 μg/ml) against Staphylococcus aureus biofilm. Compound 4b-4h showed equal antibiofilm activity against Staphylococcus epidermidis compared to standard Vancomycin (MIC=3.125 μg/ml).

Marine Bromopyrrole Alkaloids: Synthesis and Diverse Medicinal Applications

Marine organisms have been found to be a very rich source of bioactive molecules. Among marine organisms, sponges have been proven to be excellent producers of secondary metabolites. More than 5,300 compounds have been isolated from sponges with around 200 new molecules reported each year. Bromopyrrole alkaloids constitute a family of exclusively marine alkaloids and represent a fascinating example of the large variety of compounds formed by marine sponges which exhibit different biological activities such as antifeedent, anti-biofilm, anticancer, antiinflammatory, antimicrobial, immunomodulatory, analgesic, antiserotonergic, antiangiogenic, antihistaminic, chitinase inhibitor and actimyosin ATPase activator. More than 140 derivatives with different structures and biological activities, have been isolated from more than 20 different sponges. Most of these alkaloids share a key building block, pyrrole-imidazole with oroidin being their underlying structural motif. In this review detailed account of isolation and medicinal application of marine bromopyrrole alkaloids and their synthetic derivatives are discussed.

Design and synthesis of novel carbazolo–thiazoles as potential anti-mycobacterial agents using a molecular hybridization approach

Various substituted carbazolo–thiazoles (compounds 6a–6o) were synthesized in good yields using a molecular hybridization approach. The synthesized compounds were evaluated for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain at the National Institute of Allergy and Infectious Diseases (Bethesda, MD, USA). Among the tested series, compound 6c (minimum inhibitory concentration 21 μM) showed the most promising anti-mycobacterial activity. Brief structure–activity relationship studies showed that the electron-donating groups (OCH3 and OH), particularly on the phenyl ring of the thiazole motif, had a positive correlation with the anti-mycobacterial activity. In addition, they displayed low cytotoxicity against a mammalian Vero cell line using the MTT assay, thereby having a high therapeutic index. This study shows the importance of molecular hybridization and the scope for the development of carbazole–thiazole compounds as potential anti-mycobacterial agents.

Synthesis of novel 4-nitropyrrole-based semicarbazide and thiosemicarbazide hybrids with antimicrobial and anti-tubercular activity.

We report the synthesis and screening of forty novel 4-nitropyrrole-semicarbazide conjugates inspired from the reported bio-potential of bromopyrrole alkaloids and semicarbazide derivatives for antimicrobial activity. Herein, hybrids 5k-5o, 5r, 5s and 5t displayed four-fold increased activity (MIC=0.39 μg/mL) against Escherichia coli compared to standard ciprofloxacin. Eight hybrids, 5k-5o and 5r-5t displayed equal antibacterial activity (MIC=1.56 μg/mL) against Klebsiella pneumonia compared to standard ciprofloxacin. Hybrid, 5k-5o (MIC=0.195 μg/mL) displayed highly potent antibacterial activity against MSSA as compared to standard ciprofloxacin. Eight-fold superior activity was observed for four hybrids 5k-5m and 5o (MIC=0.39 μg/mL) against MRSA. Further, nine hybrids displayed four-fold superior antifungal activity (MIC=0.78 μg/mL) compared to standard Amphotericin B. Encouraging MICs of these hybrids recognize them as promising leads for development of potential antimicrobial drugs.

A Recent Perspective on Discovery and Development of Diverse Therapeutic Agents Inspired from Isatin Alkaloids

Isatin as an alkaloidal framework have consistently attracted attention of medicinal chemist towards development of wide range of novel therapeutic agents. This review report has discussed significant isatin lead molecules and their derivatives which have shown promising biological potential in recent times. The substituted isatins showing a potent pharmacological activities such as antimicrobial, antitubercular, anticancer, antioxidant, anti-histaminic, anti-HIV, antiviral, anti-inflammatory, anti-Parkinsons and antidiabetic have been described in this review. The mechanism of action leading to therapeutic activity of the respective isatin derivation has also been recorded. This review reveals that the systematic and rational modifications on isatin motif exhibited significant bio-activities which can be exploited for the development of potent novel therapeutic agents in the future studies. Hence the quest to investigate more structural alterations on isatin scaffold should be continued.

Design, synthesis and antistaphylococcal activity of marine pyrrole alkaloid derivatives.

Abstract A novel set of 16 hybrids of bromopyrrole alkaloids with aroyl hydrazone were designed, synthesized and evaluated for antibacterial and antibiofilm activities against methicillin-resistant Staphylococcus aureus (MRSA; ATCC 43866), methicillin-susceptible Staphylococcus aureus (MSSA; ATCC 35556) and Staphylococcus epidermidis (SE, S. epidermidis ATCC 35984). Of the 16 tested hybrids, 14 exhibited equal or superior antibiofilm activity against MSSA and MRSA relative to standard vancomycin. Compound 4m showed highest potency with antibiofilm activity of 0.39 µg/mL and 0.78 µg/mL against MSSA and MRSA, respectively. Thus, this compound could act as a potential lead for further development of new antistaphylococcal drugs.

Synthesis, pharmacological screening and in silico studies of new class of Diclofenac analogues as a promising anti-inflammatory agents.

A novel series of 5-[2-(2,6-dichlorophenylamino)benzyl]-3-(substituted)-1,3,4-oxadiazol-2(3H)-thione (4a-k) derivatives have been synthesized by the Mannich reaction of 5-[2-(2,6-dichlorophenylamino)benzyl]-1,3,4-oxadiazol-2(3H)-thione (3) with an appropriately substituted primary/secondary amines, in the presence of formaldehyde and absolute ethanol. Structures of these novel compounds were characterized on the basis of physicochemical, spectral and elemental analysis. The title compounds (4a-k) were screened for in vivo acute anti-inflammatory and analgesic activities at a dose of 10mg/kg b.w. Compound 4k exhibited the most promising and significant anti-inflammatory profile while compounds 4a, 4d, 4e, 4i, and 4j showed moderate to good inhibitory activity at 2nd and 4thh, respectively. These compounds were also found to have considerable analgesic activity (acetic acid induced writhing model) and antipyretic activity (yeast induced pyrexia model). In addition, the tested compounds were also found to possess less degree of ulcerogenic potential as compared to the standard NSAIDs. Compounds that displayed promising anti-inflammatory profile were further evaluated for their inhibitory activity against cyclooxygenase enzyme (COX-1/COX-2), by colorimetric COX (ovine) inhibitor screening assay method. The results revealed that the compounds 4a, 4e, 4g and 4k exhibited effective inhibition against COX-2. In an attempt to understand the ligand-protein interactions in terms of the binding affinity, docking studies were performed using Molegro Virtual Docker (MVD-2013, 6.0) for those compounds, which showed good anti-inflammatory activity. It was observed that the binding affinities calculated were in agreement with the IC50 values.