Parth Thakor

Green synthesis and pharmacological screening of polyhydroquinoline derivatives bearing a fluorinated 5-aryloxypyrazole nucleus

A novel series of polyhydroquinoline scaffolds 8a–p has been designed and synthesized under ultrasonic irradiation by a one-pot three-component cyclocondensation reaction of 3-methyl-5-substituted aryloxy-1-phenyl-1H-pyrazole-4-carbaldehydes 3a–d with malononitrile 7 and various enhydrazinoketones 6a–e in the presence of piperidine as basic catalyst. All the synthesized compounds have been characterized by various spectroscopic techniques and elemental analysis. All the synthesized compounds were evaluated for their in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain and also for their in vitro antimalarial activity against Plasmodium falciparum. Compounds 8c, 8i, 8j, 8l and 8m exhibited excellent antimalarial potency. The cytotoxicity of the synthesized compounds was tested using a bioassay of S. pombe cells at the cellular level. Compounds 8i, 8j, 8k and 8l were found to have maximum toxicity, while compounds 8e, 8m, 8c were found to be less cytotoxic. Some of them displayed luminous antibacterial activity and reasonable antituberculosis activity as compared with the first line drugs.

Synthesis of 1,3,5-trisubstituted pyrazoline derivatives and their applications

A series of 1,3,5-trisubstituted pyrazolines based homoleptic Ru(III) complexes of type [Ru(L1–7)3]·(PF6)3 (L1–7 = pyrazoline ligands) have been synthesized and characterized by elemental analysis, electronic spectroscopy, conductance measurements, thermogravimetric analysis (TGA), electron paramagnetic resonance (EPR), fourier transform infrared (FT-IR) spectroscopy and liquid chromatography mass spectroscopy (LC-MS). Octahedral geometry around ruthenium has been assigned in all complexes using EPR and electronic spectral analysis. All complexes have been investigated for their interaction with Herring Sperm (HS) DNA utilizing an absorption titration (Kb = 2.42–6.07 × 105 M−1) and viscosity measurement study. The studies suggest the classical intercalative mode of binding. The DNA-binding property of the Ru(III) complexes was also investigated theoretically using a molecular docking study and suggests an intercalation binding mode between the complex and nucleotide base pairs. A cleavage study on pUC19 DNA has been performed by agarose gel electrophoresis. The results indicated that the Ru(III) complexes can more effectively promote the cleavage of plasmid DNA. The free ligands and their complexes have been evaluated for cytotoxicity activity against S. pombe cells at a cellular level. A comparative study of cellular level cytotoxicity values of the all compounds indicates that the metal complexes show better activity against S. pombe cells compared to the pyrazoline ligands. The complexes have been screened for their in vitro antibacterial activity against two Gram(+ve) and three Gram(−ve) microorganisms. Ru(III) complexes are good in vitro cytotoxic agents and 50% lethal concentration (LC50) values are in range of 5.296–7.925 μg mL−1. All newly synthesized Ru(III) complexes have been also evaluated for their in vitro antimalarial activity against Plasmodium falciparum strain [inhibition concentration (IC50) = 0.54–0.92 μg mL−1].

Extraction and purification of phytol from Abutilon indicum: cytotoxic and apoptotic activity

Medicinal plants possess a wide range of secondary metabolites and most of these secondary metabolites have their own importance in the field of medicine. Abutilon indicum is widely used as a medicinal plant in the Indian system of medicine. In the present study, we have evaluated the apoptosis inducing ability of leaf extract of A. indicum. Hydromethanolic leaf extract showed cytotoxicity on Schizosaccharomyces pombe cells by affecting the growth and viability. Phytochemical analysis of the extract revealed the presence of secondary metabolites. A 2D TLC method was used for the separation of the active cytotoxic compound. A HPTLC method was used for the quantification of the bioactive compound. A GC-HRMS method was employed for the identification of the active principle as phytol, which was found to be responsible for inducing ROS mediated apoptosis in S. pombe.

Novel morpholinoquinoline nucleus clubbed with pyrazoline scaffolds: Synthesis, antibacterial, antitubercular and antimalarial activities.

A series of novel morpholinoquinoline based conjugates with pyrazoline moiety were synthesized under microwave irradiation. The newly synthesized compounds were screened for their preliminary in vitro antibacterial activity against a panel of pathogenic strains of bacteria and fungi, antituberculosis activity against Mycobacterium tuberculosis H37Rv and antimalarial activity against Plasmodium falciparum. Most of them exhibited significant antibacterial activity as compared to the first line drugs. Compounds 6a and 9d were found to possess excellent antibacterial activity potency as compared to ampicillin (286 μM), chloramphenicol (154 μM) and ciprofloxacin (150 μM). In antifungal screening, against Candida albicans, compounds 6c, 7c, 8a, 8b, 8c and 9b showed significant activity as compared to griseofulvin (1147 μM). Compounds 8b, 6b, 9d, 6a, 9b, 7b and 8a displayed brilliant activity against P. falciparum strain as compared to chloroquine (IC50 0.062 μM) as well as quinine (IC50 0.826 μM). Compounds 6d, 7b, 8b, 9c and 9d exhibited superior antitubercular activity. Among them 8b was found to be equipotent to rifampicin with 95% inhibition. The cytotoxicity of the synthesized compounds was tested using bioassay of Schizosaccharomyces pombe cells at cellular level.

1, 2, 4-triazole and 1, 3, 4-oxadiazole analogues: synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities

1,2,4-Triazole and 1,3,4-oxadiazole analogues are of interest due to their potential activity against microbial and malarial infections. In search of suitable antimicrobial and antimalarial compounds, we report here the synthesis, characterization and biological activities of 1,2,4-triazole and 1,3,4-oxadiazole analogues (SS 1-SS 10). The molecules were characterized by IR, mass, 1H NMR, 13C NMR and elemental analysis. The in vitro antimicrobial activity was investigated against pathogenic strains, the results were explained with the help of DFT and PM6 molecular orbital calculations. In vitro cytotoxicity and genotoxicity of the molecules were studied against S. pombe cells. In vitro antimalarial activity was studied. The active compounds were further evaluated for enzyme inhibition efficacy against the receptor Pf-DHFR computationally as well as in vitro to prove their candidature as lead dihydrofolate reductase inhibitors.

Phytol induces ROS mediated apoptosis by induction of caspase 9 and 3 through activation of TRAIL, FAS and TNF receptors and inhibits tumor progression factor Glucose 6 phosphate dehydrogenase in lung carcinoma cell line (A549)

A number of drugs as well as lead molecules are isolated from natural sources. Phytol is one of such lead molecule belongs to terpenes group distributed widely in medicinal plants. In the present work, we investigated the cytotoxic behavior of phytol on human lung carcinoma cells (A549). Phytol was found to cause characteristic apoptotic morphological changes and generation of ROS in A549 cells. The mechanism of phytol involved the activation of TRAIL, FAS and TNF-α receptors along with caspase 9 and 3. In silico molecular docking studies revealed that phytol has a good binding affinity with glucose-6-phosphate dehydrogenase (G6PD), which is known to promote tumor proliferation. The ability of phytol to become potential drug candidate has been revealed from the pharmacokinetic study performed in the present study.

Benzothiazole analogues: synthesis, characterization, MO calculations with PM6 and DFT, in silico studies and in vitro antimalarial as DHFR inhibitors and antimicrobial activities

Benzothiazole analogues are of interest due to their potential activity against malarial and microbial infections. In search of suitable antimicrobial and antimalarial agents, we report here the synthesis, characterization and biological activities of benzothiazole analogues (J 1-J 10). The molecules were characterized by IR, Mass, 1H NMR, 13C NMR and elemental analysis. The in vitro antimicrobial activity was investigated against pathogenic strains; the results were explained with the help of DFT and PM6 molecular orbital calculations. In vitro cytotoxicity and genotoxicity of the molecules were studied against S. pombe cells. In vitro antimalarial activity was studied. The active compounds J 1, J 2, J 3, J 5 and J 6 were further evaluated for enzyme inhibition efficacy against the receptor Pf-DHFR, computational and in vitro studies were carried out to examine their candidatures as lead dihydrofolate reductase inhibitors.

Bacillus species (BT42) isolated from Coffea arabica L. rhizosphere antagonizes Colletotrichum gloeosporioides and Fusarium oxysporum and also exhibits multiple plant growth promoting activity

BackgroundColletotrichum and Fusarium species are among pathogenic fungi widely affecting Coffea arabica L., resulting in major yield loss. In the present study, we aimed to isolate bacteria from root rhizosphere of the same plant that is capable of antagonizing Colletotrichum gloeosporioides and Fusarium oxysporum as well as promotes plant growth.ResultsA total of 42 Bacillus species were isolated, one of the isolates named BT42 showed maximum radial mycelial growth inhibition against Colletotrichum gloeosporioides (78%) and Fusarium oxysporum (86%). BT42 increased germination of Coffee arabica L. seeds by 38.89%, decreased disease incidence due to infection of Colletotrichum gloeosporioides to 2.77% and due to infection of Fusarium oxysporum to 0 (p < 0.001). The isolate BT42 showed multiple growth-promoting traits. The isolate showed maximum similarity with Bacillus amyloliquefaciens.ConclusionBacillus species (BT42), isolated in the present work was found to be capable of antagonizing the pathogenic effects of Colletotrichum gloeosporioides and Fusarium oxysporum. The mechanism of action of inhibition of the pathogenic fungi found to be synergistic effects of secondary metabolites, lytic enzymes, and siderophores. The major inhibitory secondary metabolite identified as harmine (β-carboline alkaloids).

Maslinic acid inhibits proliferation of renal cell carcinoma cell lines and suppresses angiogenesis of endothelial cells

Despite the introduction of many novel therapeutics in clinical practice, metastatic renal cell carcinoma (RCC) remains a treatment-resistant cancer. As red and processed meat are considered risk factors for RCC, and a vegetable-rich diet is thought to reduce this risk, research into plant-based therapeutics may provide valuable complementary or alternative therapeutics for the management of RCC. Herein, we present the antiproliferative and antiangiogenic effects of maslinic acid, which occurs naturally in edible plants, particularly in olive fruits, and also in a variety of medicinal plants. Human RCC cell lines (ACHN, Caki-1, and SN12K1), endothelial cells (human umbilical vein endothelial cell line [HUVEC]), and primary cultures of kidney proximal tubular epithelial cells (PTEC) were treated with maslinic acid. Maslinic acid was relatively less toxic to PTEC when compared with RCC under similar experimental conditions. In RCC cell lines, maslinic acid induced a significant reduction in proliferation, proliferating cell nuclear antigen, and colony formation. In HUVEC, maslinic acid induced a significant reduction in capillary tube formation in vitro and vascular endothelial growth factor. This study provides a rationale for incorporating a maslinic acid–rich diet either to reduce the risk of developing kidney cancer or as an adjunct to existing antiangiogenic therapy to improve efficacy.

Half-sandwich iridiumIII complexes with pyrazole-substituted heterocyclic frameworks and their biological applications

Low-spin IrIII organometallic half-sandwich complexes of type [(η5-C5Me5)Ir(XY)Cl]+ (XY = bipyrazoles (4a–4b)/pyrimidin-2-amines (5a–5b)/triazolo[1,5-a]pyrimidines (6a–6b)) have been synthesized and characterized. All the newly synthesized compounds have been evaluated for their DNA binding properties with calf thymus (CT DNA), which revealed enhancement in the binding constant (Kb) of the complexes. The compounds bearing an imidazole substituent proved to be better binders than compounds containing a phenoxy linkage. Molecular docking attests that π–π stacking interactions have been observed between the receptor and the compounds. Furthermore, the observed DNA cleavage potency has been ascribed to a multitarget mechanism of action of these compounds. Intriguingly, the chelation of ligands with IrIII led to a remarkable enhancement of antibacterial activity against the arbitrarily selected two Gram +ve and three Gram −ve bacterial strains. The complexes of triazolo[1,5-a]pyrimidines proved to be the most cytotoxic compounds towards brine shrimp and S. pombe cells compared to pyrazole-containing heterocyclic frameworks. All complexes showed potent cytotoxicity as compared to the ligands, with IC50 values ranging from 78 to 234 μM toward A549 human lung cancer cells. The potency of the compounds toward these cancer cells was in the order pyrimidin-2-amines > bipyrazoles > triazolopyrimidines.