Vandana S. Pore

Synthesis and antifungal activity of 1,2,3-triazole containing fluconazole analogues

Fluconazole based novel mimics containing 1,2,3-triazole were designed and synthesized as antifungal agents. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 12, 15, and 16 were found to be more potent against Candida fungal pathogens than control drugs fluconazole and amphotericin B. The studies presented here provide structural modification of fluconazole to give 1,2,3-trazole containing molecules. Furthermore, these molecules were evaluated in vivo against Candida albicans intravenous challenge in Swiss mice and antiproliferative activities were tested against human hepatocellular carcinoma Hep3B and human epithelial carcinoma A431. It was found that compound 12 resulted in 97.4% reduction in fungal load in mice and did not show any profound proliferative effect at lower dose (0.001 mg/ml).

Synthesis and antimicrobial activity of β-lactam-bile acid conjugates linked via triazole

Synthesis of novel 1,2,3-triazole-linked beta-lactam-bile acid conjugates 17-24 using 1,3-dipolar cycloaddition reaction of azido beta-lactam and terminal alkyne of bile acids in the presence of Cu(I) catalyst (click chemistry) have been realized. These molecules were evaluated in vitro for their antifungal and antibacterial activities. Most of the compounds exhibited significant antifungal and moderate antibacterial activity against all the tested strains.

Steroidal Conjugates and Their Pharmacological Applications

Nature continues to be the main source of inspiration for synthetic chemists in their quest to make novel conjugates, which can have different physical, biological and medicinal properties. Nature makes these conjugates from mixed biosynthesis and some of these chimeras are found to exhibit unusual biological properties. During the past two decades design of such entities has been receiving increasing attention. Among the hybrid natural products, hybrids of steroid frameworks have attracted great attention due to the significant biological properties and numerous therapeutic effects of steroids. The developments made over the past few years in the isolation, design and synthesis of steroidal conjugates and their pharmacological applications are discussed in this review.

Synthesis and biological evaluation of bile acid dimers linked with 1,2,3-triazole and bis-β-lactam

We report herein the synthesis and biological evaluation of bile acid dimers linked through 1,2,3-triazole and bis-beta-lactam. The dimers were synthesized using 1,3-dipolar cycloaddition reaction of diazido bis-beta-lactams , and terminal alkynes derived from cholic acid/deoxycholic acid in the presence of Cu(i) catalyst (click chemistry). These novel molecules were evaluated in vitro for their antifungal and antibacterial activity. Most of the compounds exhibited significant antifungal as well as antibacterial activity against all the tested fungal and bacterial strains. Moreover, their in vitro cytotoxicities towards HEK-293 and MCF-7 cells were also established.

Stereoselective synthesis of (22R, 23R, 24S)-3β-hydroxy-5-ene-22, 23-dihydroxy-24-methyl-cholestane : a brassinolide intermediate from 16-dehydropregnenolone acetate

Abstract A new synthesis of the important aldehyde 1 from easily available 16-Dehydropregnenolone acetate (16-DPA) in high yield is described. The aldehyde 1 is converted to trio] 24, involving a stereoselective generation of all the four chiral centers in the brassinolide side chain. The important features of this synthesis is stereospecific generation of the acetate 14 through ene reaction using three different catalysts as well as regioselective wittig reaction on the acetoxy aldehyde 20. Conversion of triol 24 to brassinolide is known, hence this constitutes a formal total synthesis of brassinolide.

Stereoselective synthesis and antimicrobial activity of steroidal C-20 tertiary alcohols with thiazole/pyridine side chain

Stereoselective synthesis of novel steroidal C-20 tertiary alcohols with thiazole and pyridine side chain using Grignard reaction of steroidal ketones and thiazole/pyridine magnesium bromide have been realized. These molecules were evaluated in vitro for their antifungal and antibacterial activities. Most of the compounds exhibited significant antifungal and antibacterial activity against all the tested strains.

Synthesis of chimeric tetrapeptide-linked cholic acid derivatives: impending synergistic agents

Tetrapeptides derived from glycine and beta-alanine were hooked at the C-3beta position of the modified cholic acid to realize novel linear tetrapeptide-linked cholic acid derivatives. All the synthesized compounds were tested against a wide variety of microorganisms (gram-negative bacteria, gram-positive bacteria and fungi) and their cytotoxicity was evaluated against human embryonic kidney (HEK293) and human mammary adenocarcinoma (MCF-7) cell lines. While relatively inactive by themselves, these compounds interact synergistically with antibiotics such as fluconazole and erythromycin to inhibit growth of fungi and bacteria, respectively, at 1-24 microg/mL. The synergistic effect shown by our novel compounds is due to their inherent amphiphilicity. The fractional inhibitory concentrations reported are comparable to those reported for Polymyxin B derivatives.

Synthesis and antifungal activity of 1,5-disubstituted-1,2,3-triazole containing fluconazole analogues

Fluconazole based novel mimics containing 1,5-disubstituted 1,2,3-triazoles were synthesized by using Ru catalysed 1,3 dipolar cycloaddition. All the newly synthesized compounds and pure enantiomers were more potent than fluconazole against Candida albicans. Docking of 9A and 9B showed different conformation in the active site of Cyp51 of Candida albicans. The more active compounds 2 and 2A did not exhibit any toxicity up to 3.12 μg mL−1 against mammalian cell line L929.

Design and synthesis of bile acid-based amino sterols as antimicrobial agents.

New bile acid-based amino sterols were synthesized in good yields from C-3beta-oxiranes as key intermediates. These derivatives were evaluated for their in vitro antimicrobial properties against human pathogens. These compounds showed better antibacterial activity as compared to antifungal activity. Compounds 21 and 22 showed comparable antibacterial activity to gentamicin against Staphylococcus aureus with IC50 values of 5.14 and 4.46 microg/mL. This is the first report for the synthesis of C-3beta-oxiranes on the steroids having A/B cis ring junction and these oxiranes have been used for the synthesis of amino sterols 17, 18, 21, and 22.

STEREOSELECTIVE SYNTHESIS OF A NEW HEXANOR(C23-C28)CASTASTERONE-20,22-ETHYL DIETHER FROM 16-DEHYDROPREGNENOLONE ACETATE AND ITS PLANT GROWTH PROMOTING ACTIVITY

Abstract Stereoselective synthesis of a new hexanor(C23–C28)castasterone-20,22-ethyl diether 22 has been achieved in sixteen steps from cheap and readily available 16-dehydropregnenolone acetate. This new brassinosteroid has shown typical brassin activity in mung bean epicotyl bioassay.