Biomedical subjects

Shabana I Khan

Publications and source records attributed to Shabana I Khan.

At least 19 recordsLinked to original sources

PubMed2006

Synthesis, antifungal activity, and structure-activity relationships of coruscanone A analogues.

Coruscanone A, a plant-derived cyclopentenedione derivative, showed potent in vitro antifungal activity against Candida albicans and Cryptococcus neoformans comparable to amphotericin B and fluconazole. A series of analogues have been synthesized by modification of the cyclopentenedione ring, the enolic methoxy functionality, and the side chain styryl moiety of this natural product lead. A structurally close 1,4-benzoquinone analogue was also prepared. All the compounds were examined for their in vitro activity against major opportunistic fungal pathogens including C. albicans, C. neoformans, and Aspergillus fumigatus and fluconazole-resistant C. albicans strains, with several analogues demonstrating potent antifungal activity. Structure-activity relationship studies indicate that the 2-methoxymethylenecyclopent-4-ene-1,3-dione structural moiety is the pharmacophore responsible for the antifungal activity of this class of compounds while the side chain styryl-like moiety plays an important complementary role, presumably contributing to target binding.

Animals↗

PubMed2006

Characterization of volatile constituents of Scaligeria tripartita and studies on the antifungal activity against phytopathogenic fungi.

The chemical composition of the essential oils obtained from stems and leaves, fruits and roots of Scaligeria tripartita oil was analyzed by gas chromatography-mass spectrometry. A total of 38 compounds were identified ranging 89-94% of the oil samples. Geijerene was found as a main compound in the oils of the stems and leaves (37%) and fruits (55%), whereas epoxypseudoisoeugenol angelate (37%) was found as a main compound in the root oil. Oils were subsequently evaluated for their antimalarial, antimicrobial against human pathogenic bacteria or fungi and antifungal activities against plant pathogens. Antifungal activity of Scaligeria oils was observed against the strawberry anthracnose-causing fungal plant pathogens Colletotrichum acutatum, C. fragariae and C. gloeosporioides using the direct overlay bioautography assay. Chemotaxonomically important pure compounds indicated in the bioautography assay were subsequently evaluated in a 96-well microdilution broth assay. The performance of overpressured layer chromatography (OPLC) and TLC for the analysis of Scaligeria essential oils was also compared.

Antifungal Agents↗

PubMed2006

Inhibition of NF-kappaB-mediated transcription and induction of apoptosis by melampolides and repandolides.

PURPOSE: Nuclear factor-kappaB (NF-kappaB) plays a crucial role in the regulation of inflammatory processes, cell proliferation, and apoptosis. Blocking NF-kappaB signaling may represent a therapeutic strategy in cancer and inflammation therapy. The aim of this study was to investigate the effects of sesquiterpenes isolated from Asteraceae, namely melampolides (enhydrin, tetraludin A) and repandolides (repandins A, B, D and E) on the activation of NF-kappaB, cell growth of cancer cells, cell cycle progression and apoptosis. In addition, their effects on the activity of cyclooxygenase-2 (COX-2) enzyme were also evaluated. METHODS: Cell-based reporter gene assay was conducted in SW1353 cells. COX-2 enzyme activity and cell growth inhibition was determined by enzyme immunoassay and MTT assay respectively. Cell cycle analysis was carried out by flow cytometry and apoptosis was observed by DAPI staining assay. RESULTS: In SW1353 cells, transcription mediated by NF-kappaB was inhibited by enhydrin, tetraludin A and repandins A, B, D and E, while Sp-1 mediated transcription was not affected. COX-2 enzyme activity was inhibited by enhydrin, repandin A and E, but not by tetraludin A, repandin B and D. These compounds were effective in inhibiting the growth of a panel of human tumor cell lines in a concentration-dependent manner. Cell cycle analysis and DAPI staining indicated cell cycle arrest in G(2)/M phase and induction of apoptosis. CONCLUSIONS: Enhydrin, tetraludin A and repandins A, B, D and E inhibited tumor cell growth and induced cell cycle arrest and apoptosis. These effects may be related to inhibition of NF-B activation.

Apoptosis↗

PubMed2006

9,10-seco-9,19-Cyclolanostane arabinosides from the roots of Actaea podocarpa.

Seven 9,10-seco-9,19-cyclolanostane arabinosides, named podocarpasides A-G (1-7), were isolated from the roots of Actaea podocarpa DC., a species closely related to black cohosh (a well known dietary supplement). Their structures were determined with the help of spectroscopic data including extensive 2D NMR spectroscopy. The isolates were found inactive, when tested for cytotoxic, estrogenic, and antioxidant activities in cell based assays. They were also tested for anticomplement activity against the classical pathway of complement system and only podocarpaside C (3) inhibited modest complement activity with an IC50 value of 200 microM.

Carbohydrate Conformation↗

PubMed2006

Podocarpaside, a triterpenoid possessing a new backbone from Actaea podocarpa.

Podocarpaside (1), a novel arabinoside possessing a unique triterpene skeleton was isolated from Actaea podocarpa, a closely related species to black cohosh (dietary supplement used for menopausal disorders). Podocarpaside belongs to a new class of triterpenoids, for which the name "ranunculane" is proposed. Compound 1 possesses anticomplement activity. [structure: see text].

Actaea↗

PubMed2006

Synthesis, antimalarial, antileishmanial, antimicrobial, cytotoxicity, and methemoglobin (MetHB) formation activities of new 8-quinolinamines.

We report the synthesis, in vitro antiprotozoal (against Plasmodium and Leishmania), antimicrobial, cytotoxicity (Vero and MetHb-producing properties), and in vivo antimalarial activities of two series of 8-quinolinamines. N1-{4-[2-(tert-Butyl)-6-methoxy-8-quinolylamino]pentyl}-(2S/2R)-2-aminosubstitutedamides (21-33) and N1-[4-(4-ethyl-6-methoxy-5-pentyloxy-8-quinolylamino)pentyl]-(2S/2R)-2-aminosubstitutedamides (51-63) were synthesized in six steps from 6-methoxy-8-nitroquinoline and 4-methoxy-2-nitro-5-pentyloxyaniline, respectively. Several analogs displayed promising antimalarial activity in vitro against Plasmodium falciparum D6 (chloroquine-sensitive) and W2 (chloroquine-resistant) clones with high selectivity indices versus mammalian cells. The most promising analogs (21-24) also displayed potent antimalarial activity in vivo in a Plasmodium berghei-infected mouse model. Most interestingly, many analogs exhibited promising in vitro antileishmanial activity against Leishmania donovani promastigotes, and antimicrobial activities against a panel of pathogenic bacteria and fungi. Several analogs, notably 21-24, 26-32, and 60, showed less MetHb formation compared to primaquine indicating the potential of these compounds in 8-quinolinamine-based antimalarial drug development.

Aminoquinolines↗

PubMed2006

Antiprotozoal and antimicrobial activities of O-alkylated and formylated acylphloroglucinols.

In the present article, we examined the antileishmanial, antimalarial, antibacterial, and antifungal activities of several newly synthesized O-alkylated phloroglucinol compounds (11-19) which are analogues of the naturally occurring antimalarial compound 1. Analogues 12 and 16 exhibited antileishmanial activity against, Leishmania donovani promastigotes with IC(50)s of 5.3 and 4.2microg/mL, respectively. Naturally occurring monomeric formylated acylphloroglucinol compounds, grandinol (2), jensenone (3), and their analogues (29-37), were also synthesized and evaluated for antileishmanial, antimalarial, antibacterial, and antifungal activities. Amongst these, both grandinol and jensenone showed mild to moderate antibacterial, antifungal, and antileishmanial activities. Jensenone (3) was effective against Candida albicans with an IC(50) of 5.5microg/mL but was ineffective against Cryptococcus neoformans and methicillin-resistant Staphylococcus aureus. Among the analogues, 34 was the most active against C. albicans and C. neoformans with IC(50)s of 2.0 and 2.5microg/mL, respectively, and was fungicidal toward Candida albicans.

Animals↗

PubMed2006

Phytochemical study of actaea rubra and biological screenings of isolates.

A phytochemical study on the chemical constituents of the roots of Actaea rubra led to the isolation and characterization of eleven xylosides of 9,19-cyclolanostane type triterpenes including the new rubraside A (1) and a beta-sitosterol glucoside. The structures of the isolates were determined with the help of spectroscopic data including 2-dimensional NMR as well as comparison with reported data. The compounds were tested for cytotoxic, estrogenic, antioxidant, and anticomplement activities. They were found inactive in the tested assays, except for 4, which showed moderate anticomplement activity.

Actaea↗

PubMed2006

Chemical composition and antifungal activity of Salvia macrochlamys and Salvia recognita essential oils.

Essential oils of Salvia macrochlamys and Salvia recognita were obtained by hydrodistillation of dried aerial parts and characterized by gas chromatography and gas chromatography-mass spectrometry. One hundred and twenty identified constituents representing 97.7% in S. macrochlamys and 96.4% in S. recognita were characterized, and 1,8-cineole, borneol, and camphor were identified as major components of the essential oils. The oils were evaluated for their antimalarial, antimicrobial, and antifungal activities. Antifungal activity of the essential oils from both Salvia species was nonselective at inhibiting growth and development of reproductive stroma of the plant pathogens Colletotrichum acutatum, Colletotrichum fragariae, and Colletotrichum gloeosporioides. S. macrochlamys oil had good antimycobacterial activity against Mycobacterium intracellulare; however, the oils showed no antimicrobial activity against human pathogenic bacteria or fungi up to a concentration of 200 microg/mL. S. recognita oil exhibited a weak antimalarial activity against Plasmodium falciparum.

Anti-Infective Agents↗

PubMed2006

Atropurosides A-G, new steroidal saponins from Smilacina atropurpurea.

Atropurosides A-G (1-7), seven new steroidal saponins, which possess new polyhydroxylated aglycones, were isolated from the rhizomes of Smilacina atropurpurea (Convallariaceae), together with a known saponin, dioscin (8). Their structures were elucidated on the basis of detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical methods. Antifungal testing of the eight compounds indicated that atropurosides B (2) and F (6) were fungicidal against Candida albicans, Candida glabrata, Cryptococcus neoformans, and Aspergillus fumigatus with minimum fungicidal concentrations (MFCs) < or = 20 microg/ml, while dioscin (8) was selectively active against C. albicans and C. glabrata (MFC < or = 5.0 microg/ml). Furthermore, the antifungal saponins 2, 6, and 8 were evaluated for their in vitro cytotoxicities in a panel of human cancer cell lines (SK-MEL, KB, BT-549, SK-OV-3, and HepG2) and non-cancerous Vero cells. All showed moderate cytotoxicities. It appears that the antifungal activity of these steroidal saponins correlates with their cytotoxicity against mammalian cells.

Animals↗

PubMed2006

Schisandrene, a dibenzocyclooctadiene lignan from Schisandra chinensis: structure-antioxidant activity relationships of dibenzocyclooctadiene lignans.

Phytochemical investigation of the fruits of Schisandra chinensis led to the isolation of 13 lignans including schisandrene (13), a new lignan based on a dibenzocyclooctadiene backbone with an exocyclic double bond. Its structure and absolute configuration were established using NMR, MS, and CD data. Antioxidant activity of the lignans was evaluated using a DCFH-DA cellular-based assay. The structure-activity relationships of the dibenzocyclooctadiene lignans showed that the exocyclic methylene functionality was essential for antioxidant activity, with the benzoyloxy group probably enhancing such effects.

Antioxidants↗

PubMed2006

Capisterones A and B, which enhance fluconazole activity in Saccharomyces cerevisiae, from the marine green alga Penicillus capitatus.

A whole-cell-based assay using Saccharomyces cerevisiae strains that overexpress Candida albicans CDR1 and MDR1 efflux pumps has been employed to screen natural product extracts for reversal of fluconazole resistance. The tropical green alga Penicillus capitatus was selected for bioassay-guided isolation, leading to the identification of capisterones A and B (1 and 2), which were recently isolated from this alga and shown to possess antifungal activity against the marine pathogen Lindra thallasiae. Current work has assigned their absolute configurations using electronic circular dichroism and determined their preferred conformations in solution based on detailed NOE analysis. Compounds 1 and 2 significantly enhanced fluconazole activity in S. cerevisiae, but did not show inherent antifungal activity when tested against several opportunistic pathogens or cytotoxicity to several human cancer and noncancerous cell lines (up to 35 microM). These compounds may have a potential for combination therapy of fungal infections caused by clinically relevant azole-resistant strains.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Aromatic constituents of Uvaria grandiflora.

Grandiuvarone A (1) and grandiuvarins A-C (2-4) were isolated from the bark of Uvaria grandiflora. The structures of these new aromatic compounds were elucidated on the basis of spectroscopic analyses, especially 2D NMR techniques. Only compound 1 exhibited antileishmanial activity, with IC(50)/IC(90) values of 0.7/1.5 microg/mL. The positive controls pentamidine and amphotericin B had IC(50)/IC(90) values of 1.6/6.6 and 0.17/0.34 microg/mL, respectively.

Amphotericin B↗

PubMed2006

Manzamine B and E and ircinal A related alkaloids from an Indonesian Acanthostrongylophora sponge and their activity against infectious, tropical parasitic, and Alzheimer's diseases.

Four new manzamine-type alkaloids, 12,28-oxamanzamine E (2), 12,34-oxa-6-hydroxymanzamine E (3), 8-hydroxymanzamine B (5), and 12,28-oxaircinal A (11), were isolated from three collections of an Indonesian sponge of the genus Acanthostrongylophora together with 13 known manzamine alkaloids, ircinal A, ircinol A, xestomanzamine A, manzamines A, E, F, J, and Y, manadomanzamines A and B, neo-kauluamine, 8-hydroxymanzamine A, and manzamine A N-oxide. The structures of the new compounds were elucidated by means of 1D and 2D NMR spectroscopic methods. Three of these compounds (2, 3, and 11) possess a unique manzamine-type aminal ring system generated through an ether linkage between carbons 12-28 or between carbons 12-34. In the case of manzamine B and related metabolites, carbons 11 and 12 of the typical manzamine structure have an epoxide group and add to our growing understanding of manzamine structure-activity relationships (SAR) and metabolism. The bioactivity and SAR for a number of previously reported manzamine-related metabolites against malaria, leishmania, tuberculosis, and HIV-1 are also presented. Manzamine Y (9) showed significant inhibitory activity of GSK3, an enzyme implicated in Alzheimer's disease pathology. The toxicity of manzamine A and neo-kauluamine was evaluated against both medaka fry and eggs.

Alzheimer Disease↗

PubMed2006

Antifungal activity of C-27 steroidal saponins.

As part of our search for new antifungal agents from natural resources, 22 C-27 steroidal saponins and 6 steroidal sapogenins isolated from several monocotyledonous plants were tested for their antifungal activity against the opportunistic pathogens Candida albicans, Candida glabrata, Candida krusei, Cryptococcus neoformans, and Aspergillus fumigatus. The results showed that the antifungal activity of the steroidal saponins was associated with their aglycone moieties and the number and structure of monosaccharide units in their sugar chains. Within the 10 active saponins, four tigogenin saponins (compounds 1 to 4) with a sugar moiety of four or five monosaccharide units exhibited significant activity against C. neoformans and A. fumigatus, comparable to the positive control amphotericin B. The antifungal potency of these compounds was not associated with cytotoxicity to mammalian cells. This suggests that the C-27 steroidal saponins may be considered potential antifungal leads for further preclinical study.

Animals↗

PubMed2006

Anti-plasmodial and anti-leishmanial activity of conformationally restricted pentamidine congeners.

A library of 52 pentamidine congeners in which the flexible pentyldioxy linker in pentamidine was replaced with various restricted linkers was tested for in-vitro activity against two Plasmodium falciparum strains and Leishmania donovani. The tested compounds were generally more effective against P. falciparum than L. donovani. The most active compounds against the chloroquine-sensitive (D6, Sierra Leone) and -resistant (W2, Indochina) strains of P. falciparum were bisbenzamidines linked with a 1,4-piperazinediyl or 1, 4-homopiperazinediyl moiety, with IC50 values (50% inhibitory concentration, inhibiting parasite growth by 50% in relation to drug-free control) as low as 7 nM based on the parasite lactate dehydrogenase assay. Seven piperazine-linked bisbenzamidines substituted at the amidinium nitrogens with a linear alkyl group of 3-6 carbons (22, 25, 27, 31) or cycloalkyl group of 4, 6 or 7 carbons (26, 32, 34) were more potent (IC50<40 nM) than chloroquine or pentamidine as anti-plasmodial agents. The most active anti-leishmanial agents were 4,4'-[1,4-phenylenebis(methyleneoxy)]bisbenzenecarboximidamide (2, IC50 approximately 0.290 microM) and 1,4-bis[4-(1H-benzimidazol-2-yl)phenyl] piperazine (44, IC50 approximately 0.410 microM), which were 10- and 7-fold more potent than pentamidine (IC50 approximately 2.90 microM). Several of the more active anti-plasmodial agents (e.g. 2, 31, 33, 36-38) were also potent anti-leishmanial agents, indicating broad antiprotozoal properties. However, a number of analogues that showed potent anti-plasmodial activity (1, 18, 21, 22, 25-28, 32, 43, 45) were not significantly active against the Leishmania parasite. This indicates differential modes of anti-plasmodial and anti-leishmanial actions for this class of compounds. These compounds provide important structure-activity relationship data for the design of improved chemotherapeutic agents against parasitic infections.

Animals↗

PubMed2005

Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities of euglobals and their analogues.

In the present communication, naturally occurring phloroglucinol-monoterpene adducts, euglobals G1-G4 (3b/a and 4a/b) and 16 new analogues (13a/b-18a/b and 19-22) were synthesized by biomimetic approach. These synthetic compounds differ from natural euglobals in the nature of monoterpene and acyl functionality. All of these compounds were evaluated for their antibacterial, antifungal, antileishmanial and antimalarial activities. Analogue 17b possessed good antibacterial activity against methicillin-resistant Staphylococcus aureus, while analogues 19-22 possessed potent antifungal activity against Candida glabrata with IC50s ranging from 1.5 to 2.5 microg/mL. Euglobals along with all synthesized analogues exhibited antileishmanial activity. Amongst these, euglobal G2 (3a), G3 (4a) and analogues 13a and 14a showed potent antileishmanial activity with IC50s ranging from 2.8 to 3.9 microg/mL. Analogue 16a possessed antimalarial activity against chloroquine sensitive D6 clone of Plasmodium falciparum. None of the compounds showed toxicity against mammalian kidney fibroblasts (vero cells) upto the concentration of 4.76 microg/ml.

Animals↗

PubMed2005

Design and synthesis of low molecular weight compounds with complement inhibition activity.

An attempt was made to synthesize a series of non-cytotoxic low molecular weight compounds of varying substitutions and functionalities having pharmacophore activity like carbonyl compounds, carboxylic acid and bioisosteres like tetrazole and phenyl acrylic acid. The in vitro assay of these analogues for the inhibition of complement activity revealed significant inhibitory activity for varying substituents and, particularly, for bioisosteres, that is, tetrazole and phenyl acrylic acid derivatives.

Acrylates↗