Muzammil M. Mansuri

Synthesis and in vitro evaluation of a phosphonate prodrug: bis(pivaloyloxymethyl) 9-(2-phosphonylmethoxyethyl)adenine

9-(2-Phosphonylmethoxyethyl)adenine (PMEA; 1) was acylated with chloromethyl pivalate to afford bis(pivaloyloxymethyl) PMEA (2). The ester prodrug demonstrated enhanced in vitro potency against HSV-2 greater than 150-fold higher than the parent compound. The antiviral activity of 2 was 50-fold better than PMEA against HSV-1, and equipotent against HIV and HCMV. The toxicity of 2 was studied in both resting and growing cells.

Preparation of the geometric isomers of DDC, DDA, D4C and D4T as potential anti-HIV agents

Abstract β-L-ddC ( 5 ), β-L-ddA ( 7 ), β-L-d4T ( 7 ) and β-L-d4C ( 8 ) (enantiomers of natural dideoxynucleoside analogues with known potent HIV activity) were prepared as potential anti-HIV agents.

Structure–activity relationship studies of flavopiridol analogues

Cyclin dependent kinases (CDKs) along with the complementary cyclins form key regulatory checkpoint controls on the cell cycle. Flavopiridol is a synthetic flavone that shows potent and selective cyclin-dependent kinase inhibitory activity. In this paper, we report modifications of the 3-hydroxy-1-methylpiperidinyl (D ring) of flavopiridol and their effect on CDK inhibitory activity.

Synthesis and Antiviral Evaluation of 3′-Branched Nucixoside Analogues

Abstract A common structural feature shared by the representative nucleoside analogues active against HIV is the lack of hydroxyl substituents at the positions C -2′ and C-3′ of the furanose ring.1 These analogues which include AZT, ddI, D4T, ddC, 3′Fddt, are first converted to their 5′-0- triphosphates, which then exert their biological effect either as reverse transcriptase (RT) inhibitors or chain tetminators or both.2

Role of Retinoic Acid Receptor Gamma in the Rhino Mouse and Rabbit Irritation Models of Retinoid Activity

The three retinoic acid receptors (RAR alpha, RAR beta and RAR gamma) are known to modulate the transcription of target genes through interaction of the individual receptors with their naturally occurring ligand, retinoic acid (RA). Since RA has multiple effects in vivo, considerable effort has recently been devoted to finding selective compounds to elucidate the functions of individual receptors and to relate these functions to specific in vivo effects. The racemic synthetic retinoid 6-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)hydroxy-methyl]-2- naphthalene carboxylic acid has recently been identified as an RAR gamma-selective agonist. A synthetic method involving lipase-mediated transformation has been developed to prepare the individual enantiomers. Discrimination between the two enantiomers is seen in both transcriptional activity and binding to recombinant receptors with the (S)-enantiomer being the more active. Differences between the two compounds are also seen in the Rhino mouse utriculi reduction assay and the rabbit irritation model. In both animal models, the (S)-enantiomer consistently gave a greater response. Taken together, these results suggest that the activity and irritation seen with RA and related compounds is receptor mediated. Further, the strong selectivity of the compounds reported here for RAR gamma suggests that this receptor plays an important role in these in vivo biological activities. The discrimination between these enantiomers may be useful in the design of novel retinoids with uniquely defined biological properties.

Synthesis and structure-activity relationship of C-3 quaternary ammonium cephalosporins exhibiting anti-MRSA activities

Abstract A series of cephalosporins bearing C-3 quaternary ammonium groups were prepared and evaluated for their anti-MRSA activity. They exhibit good to excellent in vitro activity (MICs = 1−8 μg/mL) against MRSA.

Synthesis and structure-activity relationship of C-3 benzoyloxymethyl cephalosporins exhibiting anti-MRSA activities

Abstract A series of cephalosporins bearing C-3 benzoyloxymethyl groups were prepared and evaluated for their anti-MRSA activity and plasma stability. They exhibit excellent in vitro activity (MIC = 0.06 ∼2 μg/mL) against MRSA and excellent stability in human plasma.

Structural modifications of 6-naphthalene-2-carboxylate retinoids

Abstract The keto linker of 2-naphthoate retinoid 1 has been found nonessential for RAR transactivation activity and can be replaced with heteroatoms such as S, O, N without significant reduction of the activity. On the other hand, substitutions on the aromatic rings of retinoids 1 and 2 resulted in analogs with reduced potentcy and RAR selectivity.

APPLICATION OF THE HECK REACTION IN THE SYNTHESIS OF TRUNCATED NAPHTHOIC ACID RETINOIDS

Abstract A series of truncated naphthoic acid retinoids have been prepared using the Heck reaction. These retinoids were evaluated in the RAR transactivation assay in vitro and in the utriculi reduction assay in vivo. It has been found that the naphthalene ring of the retinoids is crucial for their retinoid activity and receptor selectivity.

Synthesis of 1,3-diamino-2-hydroxypropane derivatives as pseudosymmetric HIV protease inhibitors

Abstract A facile synthesis of a series of potential pseudosymmetric HIV-protease inhibitors containing 1,3-diamino-2-hydroxypropane moiety is described.