Mushtaq A. Qurishi

Synthesis of 3,5‐Diphenyl‐1H‐Pyrazoles

Abstract An efficient and convenient synthesis of 3,5‐diphenyl‐1H‐pyrazoles from chalcones by the action of hydrazine hydrate on chalcone‐epoxide followed by simultaneous dehydration is reported.

Chemical composition, antioxidant and antibacterial activities of the leaf essential oil of Juglans regia L. and its constituents

The essential oil from the leaves of Juglans regia L. (Juglandaceae) growing wild in Kashmir (India) was obtained by hydrodistillation and analysed by a combination of capillary GC-FID and GC-MS. A total of 38 compounds, representing 92.7% of the oil, were identified and the major components were found to be α-pinene (15.1%), β-pinene (30.5%), β-caryophyllene (15.5%) germacrene D (14.4%) and limonene (3.6%). The essential oil and the main individual constituents were screened for antibacterial activity and the essential oil evaluated for antioxidant activity. Antibacterial activity was evaluated using the disc diffusion and microdilution methods against a group of clinically significant Gram-positive (Staphylococcus epidermidis MTCC-435, Bacillus subtilis MTCC-441, Staphylococcus aureus) and Gram-negative bacteria (Proteus vulgaris MTCC-321, Pseudomonas aeruginosa MTCC-1688, Salmonella typhi, Shigella dyssenteriae, Klebsiella pneumonia and Escherichia coli). The essential oil and its major components exhibited broad spectrum inhibition against all the bacterial strains with Gram-positive being more susceptible to the oil than Gram-negative bacteria. Antioxidant activity of the oil was evaluated by the scavenging effect on DPPH (2,2-diphenyl-1-picrylhydrazyl) and hydroxyl radicals. In general, the essential oil exhibited high antioxidant activity which was comparable to the reference standards at the same dose (ascorbic acid and butylated hydroxyl toluene, BHT) with IC(50) values of 34.5 and 56.4μg/ml calculated by DPPH and hydroxyl radical scavenging assays respectively.

Evaluation of antioxidant and antimicrobial activities of Bergenin and its derivatives obtained by chemoenzymatic synthesis

Bergenin pentacetate (2), a peracetate derivative of biologically active lead compound Bergenin (1) isolated from Bergenia stracheyi was subjected to lipase catalyzed regioselective alcoholysis to obtain 3,4,10,11-tetracetate of Bergenin (3). The free hydroxyl group of 3 was derivatised using higher carboxylic acids to obtain acyl derivatives (4-7). These compounds synthesized via chemoenzymatic route were characterized using 1H NMR, 13C NMR and mass spectral data and evaluated for DPPH radical scavenging, antimicrobial and xanthine oxidase inhibitory activities. The studies revealed that biological activity of Bergenin can be optimized by selective modification of its structure.

Immunomodulatory activity of isoflavones isolated from Iris germanica (Iridaceae) on T-lymphocytes and cytokines.

The immunomodulatory activities of two isoflavones, 5,7‐dihydroxy‐6,4′‐dimethoxyisoflavone (irisolidone) (1) and 5,4′‐dihydroxy‐6,7‐methylenedioxyisoflavone (irilone) (2) isolated from Iris germanica (Iridaceae) is reported. Their influence on production of T‐lymphocytes (CD4+ and CD8+ cells) and T‐cell cytokines, namely Th1: IL‐2, IFN‐γ and Th2: IL‐4 and IL‐5 in a dose‐dependent manner was studied by flow cytometric method in Balb/c mice. Oral administration of drugs at doses of 0.1–0.8 mg/kg per oral dose showed 1 to possess stimulatory activity on T‐cells and Th1 cytokine production, while as 2 acted as an immunosuppressant for both cells and cytokines. The methylated products of 1 and 2 showed a similar trend to that of their parent compounds but their activity was drastically decreased revealing the importance of free phenolic groups for their immunomodulating activities. Copyright

Click chemistry inspired synthesis and bioevaluation of novel triazolyl derivatives of osthol as potent cytotoxic agents.

A new series of diverse triazoles linked through the hydroxyl group of lactone ring opened osthol (1) were synthesized using click chemistry approach. All the derivatives were subjected to 3-(4,5-Dimethylthiazol-yl)-diphenyl tetrazoliumbromide (MTT) cytotoxicity screening against a panel of seven different human cancer cell lines viz. colon (colo-205), colon (HCT-116), breast (T47D), lung (NCI-H322), lung (A549), prostate (PC-3) and Skin (A-431) to check their cytotoxic potential. Interestingly, among the tested molecules, most of the analogs displayed better cytotoxic activity than the parent osthol (1). Of the synthesized triazoles, compounds 8 showed the best activity with IC50 of 1.3, 4.9, 3.6, 41.0, 35.2, 26.4 and 7.2 μM against colon (Colo-205 and HCT-116), breast (T47D), lung (NCI-H322 and A549), prostate (PC-3) and Skin (A-431) cancer lines respectively. Compound 8 induced potent apoptotic effects in Colo-205 cells. The population of apoptotic cells increased from 11.4% in case of negative control to 24.1% at 25 μM of 8. Compound 8 also induced a remarkable decrease in mitochondrial membrane potential (ΛΨm) leading to apoptosis of cancer cells used. The present study resulted in identification of broad spectrum cytotoxic activity of analogs bearing electron withdrawing substituents, besides the enhanced selective activity of analogs with electron donating moieties.

Comparative GC–FID and GC–MS analysis of the mono and sesquiterpene secondary metabolites produced by the field grown and micropropagated plants of Artemisia amygdalina Decne

The essential oil obtained by hydrodistillation from the leaves of micropropagated plants of Artemisia amygdalina was analyzed by capillary GC–FID and GC–MS and compared with that obtained from the leaves of field growing parent plants. The oil yield from the micropropagated plants was lower (0.05% v/w) than the oil yield obtained from field-grown plants (0.2% v/w). The major constituents of the field-grown plants were p-cymene (21.0%), 1,8-cineole (24.9%), α-terpineol (5.9%), β-caryophyllene (4.7%), germacrene D (4.0%), while as the major constituents from the micropropagated plants were p-cymene (11.3%),1,8-cineole (10.2%), borneol (7.9%), α-longipinene (5.5%), α-copaene (5.5%) and β-caryophyllene (17%). The essential oil from field-grown plant was dominated by the presence of oxygenated monoterpenes (41.5%), monoterpene hydrocarbons (35.9%) and sesquiterpene hydrocarbons (16.3%) while as the essential oil of micropropagated plants was characterized by sesquiterpene hydrocarbons (40.0%), oxygenated monoterpenes (25.2%) and monoterpene hydrocarbons (21.6%).

Chemical composition and antimicrobial activity of the leaf essential oil of Skimmia laureola growing wild in Jammu and Kashmir, India

The analysis of Skimmia laureola hydrodistillate by gas chromatography coupled with mass spectrometry revealed the presence of 20 constituents, representing 94.6% of the total oil. The major constituents of oil were linalyl acetate (33.0%), linalool (25.0%), limonene (8.1%), α-terpineol (5.9%) and geranyl acetate (5.9%). The monoterpene (93.4%) rich essential oil was evaluated for its antibacterial and antifungal activities against seven microorganisms by agar diffusion and microdilution methods. The oil showed appreciable antimicrobial effects against all Gram-positive bacteria tested, including methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis with MIC values 32 and 64 µg mL−1, respectively. The oil also exhibited strong fungicidal activity against Aspergillus niger and Penicillium chrysogenum with MIC value in the range 32–16 µg mL−1. The oil could be used in the formulation of antimicrobial agents.

Isolation, Cytotoxicity Evaluation and HPLC-Quantification of the Chemical Constituents from Prangos pabularia

Phytochemical analysis of the dichloromethane:methanol (1∶1) extract of root parts of Prangos pabularia led to the isolation of twelve cytotoxic constituents, viz., 6-hydroxycoumarin (1), 7-hydroxycoumarin (2), heraclenol-glycoside (3), xanthotoxol (4), heraclenol (5), oxypeucedanin hydrate (6), 8-((3,3-dimethyloxiran-2-yl)methyl)-7-methoxy-2H-chromen-2-one (7), oxypeucedanin hydrate monoacetate (8), xanthotoxin (9), 4-((2-hydroxy-3-methylbut-3-en-1-yl)oxy)-7H-furo[3,2-g]chromen-7-one (10), imperatorin (11) and osthol (12). The isolates were identified using spectral techniques in the light of literature. 3-(4,5-dimethyl thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity screening of the isolated constituents was carried out against six human cancer cell lines including lung (A549 and NCI-H322), epidermoid carcinoma (A431), melanoma (A375), prostate (PC-3) and Colon (HCT-116) cell lines. Osthol (12) exhibited the highest cytotoxicity with IC50 values of 3.2, 6.2, 10.9, 14.5, 24.8, and 30.2 µM against epidermoid carcinoma (A431), melanoma (A375), lung (NCI-H322), lung (A549), prostate (PC-3) and colon (HCT-116) cell lines respectively. Epidermoid carcinoma cell line A431 was sensitive to most of the compounds followed by lung (A549) cancer cell line. Finally a simple and reliable HPLC method was developed (RP-HPLC-DAD) and validated for the simultaneous quantification of these cytotoxic constituents in Prangos pabularia. The extract was analyzed using a reversed-phase Agilent ZORBAX eclipse plus column C18 (4.6×250 mm, 5 µm) at 250 nm wavelength using a gradient water-methanol solvent system at a flow rate of 0.8 ml/min. The RP-HPLC method is validated in terms of recovery, linearity, accuracy and precision (intra and inter-day validation). This method, because of shorter analysis time, makes it valuable for the commercial quality control of Prangos pabularia extracts and its future pharmaceutical preparations.

Chemical composition of the essential oils of Nepeta laevigata and Nepeta elliptica from India

The genus Nepeta (Lamiaceae), also called Glechoma and Cataria, is a multiregional genus and consists of about 250 species of perennial herbs distributed in central and southern parts of Europe, Asia, and the Middle East [1–3]. These plants are commonly known as catmint [4], and about 30 species occur in India. Many Nepeta species have been reported to be biologically active and are used in folk medicine because of their spasmodic, diuretic, antiseptic, antitussive, antiasthmatic, and febrifuge activities [5–9]. Several Nepeta species are also reported to reduce serum lipids and to possess anti-inflammatory effects [10, 11]. Most Nepeta species are rich in essential oils, and various biologically active iridoids/monoterpene nepetalactones have been reported in several Nepeta species possessing diverse biological activities, viz., feline attractant, canine attractant, insect repellant, arthropod defense [12, 13], antibacterial, antifungal, and antiviral activities [14]. N. laevigata and N. elliptica are distributed through Afghanistan, China, Nepal, Pakistan, and India. In India, the two plant species are largely confined to Himachal Pradesh, Jammu and Kashmir, and Uttar Pradesh. Nepeta laevigata, also known as Betonica laevigata, is a perennial aromatic herb that grows to a height of 80 cm, is white pubescent, and has petiole 2–12 mm and leaf blade ovate to triangular, while N. elliptica is a small ascending or flexuous herb, 30–60 cm high. Both N. laevigata and N. elliptica are used in traditional medicine. Nepeta laevigata, is reported to be used locally in fevers and for sore throat, while, as an infusion of the seeds, N. elliptica is used in dysentery. According to our finding, there is no report on the chemical compostion of the essential oil of N. laevigata and N. elliptica growing in J & K, India, so the aim of the present work was to compare the chemical composition of these two Nepeta species. The chemical constituents of the volatile oils were analyzed by capillary GC-FID and GC-MS. The components of the oils of the air-dried aerial parts of N. laevigata and N. elliptica are listed in Table 1 with their percentages and relative retention indices (RRI). The different chemical constituents of the essential oils are listed in order of their elution from an RTX-5 column. As shown, 24 components belonging to different class of compounds were identified in the oil of N. laevigata, making up 86.7% of the total oil. -Citronellol (16.5%), germacrene D (19.4%), -caryophyllene (10.8%), -bisabolol oxide B (12.4%), -bourbonene (4.5%), -humulene (3.5%), spathulenol (3.9%), and -bisabolol (5.3%) were the major ones. Other constituents such as 4a,7,7a-nepetalactone (2.0%), allo-aromadendrene (1.1%), and caryophyllene oxide (3.2%) were present in small amounts. In addition, some other constituents such as -pinene, 1,8-cineole, linalool, geraniol, citronellyl acetate, etc. were present in trace amounts. The essential oil composition is dominated by the presence of sesquiterpene hydrocarbons, oxygenated sesquiterpenes, and oxygenated monoterpenes constituting 40.9%, 25.1%, and 20.7%, respectively, of the total oil composition. Of the various nepetalactone isomers, viz., 4a,7,7a-nepetalactone, 4a,7,7a-nepetalactone, and 4a,7,7a-nepetalactone, which have been labeled as the biochemical markers of the Nepeta essential oils and are very useful in chemotaxonomic studies, only one nepetalactone isomer viz., 4a, 7, 7a-nepetalactone, as a minor constituent, was present in the essential oil of Nepeta laevigata. -Caryophyllene, which is one of the major constituents of the essential oil, has been reported in some Nepeta species such as N. depauperata [15], N. flavida [16], and N. nuda [17] as the major component. Likewise, germacrene-D, the other major constituent of the oil sample, has also been reported in various other Nepeta species such as Nepeta macrosiphon [18] and Nepeta sintensii [19]. In addition, the other major components such as -bourbonene and spathulenol have been reported in N.depauperata [15], N. macrosiphon [18], and N. sintensii [19].

New isoflavones from Iris kashmiriana.

Phytochemical investigation of the rhizomes of Iris kashmiriana (Iridaceae) led to the isolation of three isoflavones characterized by 1D and 2D NMR, IR, UV, and MS as 4′-hydroxy-8-methoxy-6,7-methylenedioxyisoflavone (isonigricin, 1), 5,6-dihydroxy-4′,7-dimethoxyisoflavone (isoirisolidone, 2), and 5,7-dihydroxy-4′,6-dimethoxyisoflavone (irisolidone, 3). Compound 1 is a new isoflavone, while 2 is reported for the first time from a natural source.