Mohinder P. Mahajan

Synthesis, docking and in vitro antimalarial evaluation of bifunctional hybrids derived from β-lactams and 7-chloroquinoline using click chemistry

1,2,3-Triazole tethered β-lactam and 7-chloroquinoline bifunctional hybrids were synthesized and evaluated as potential antimalarial agents. Activity against cultured Plasmodium falciparum was dependent on the N-substituent of the β-lactam ring as well as the presence of bis-triazole at the C-3 position. The observed activity profiles were further substantiated by docking studies via inhibition of P. falciparum dihydrofolate reductase (PfDHFR), a potential target for the development of new anti-malarials.

Antiplasmodial and cytotoxicity evaluation of 3-functionalized 2-azetidinone derivatives

3-Azido-, 3-amino- and 3-(1,2,3-triazol-1-yl)-β-lactams were synthesized and evaluated for their antiplasmodial activity against four strains of Plasmodium falciparum and KB cells for their cytotoxicity profiles. The presence of a cyclohexyl substituent at N-1 and a phenyl group on the triazole ring markedly improved the activity profiles of triazole-tethered β-lactam exhibiting IC(50) values of 1.13, 1.21 and 1.00 μM against 3D7, K1 and W2 strains respectively.

Highly selective potentiometric determination of mercury(II) ions using 1-furan-2-yl-4-(4-nitrophenyl)-2-phenyl-5H-imidazole-3-oxide based membrane electrodes.

The electrode characteristics and selectivities of PVC-based mercury(II) selective coated graphite electrode (CGE) and polymeric membrane electrode (PME) incorporating the recently synthesized 1-furan-2-yl-4-(4-nitrophenyl)-2-phenyl-5H-imidazole-3-oxide are reported here. The electrodes exhibit Nernstian slope for mercury(II) ions over wide concentration ranges, i.e. 1.0 x 10(-1)M to 1.0 x 10(-6)M (with CGE) and 1.0 x 10(-1)M to 1.0 x 10(-5)M (with PME). The lower detection limits shown by CGE and PME are 8.91 x 10(-7)M and 6.30 x 10(-6)M, respectively, in the pH range of 1.0-4.0. From the comparative study of these electrodes, CGE has been found to be better than PME in terms of lower detection limit and better selectivity for mercury(II) ions with comparatively less interference from silver(I) ions. The proposed electrodes can be successfully used as an indicator electrode for potentiometric titration of mercury with potassium dichromate. The electrodes have been successfully applied for estimation of mercury content in synthetic water samples, insecticide (parad tablet) and dental amalgam.

Regioselective [4+2] cycloaddition versus nucleophilic reactions of N-arylamino substituted 1,3-diaza-1,3-butadienes with ketenes: Synthesis of pyrimidinone and fused pyrimidinone derivatives. Part II

Abstract A novel synthetic method for 3-aryl-6-phenyl-2-methylthio/secondaryamino substituted-4(3 H )-pyrimidinones 5 and 9 by the reactions of N -arylamino substituted 1,3-diaza-1,3-butadienes 1 and 6 with phenyl-, vinyl- and isopropenylketenes is explored. Semi emperical AM1 calculations on 1 and 6 are performed to explain the mechanism of their reaction with ketenes. Transformations of 5 and 9 leading to fused pyrimidinones 10 are also reported.

Synthesis and in vitro Cytotoxic evaluation of N-alkylbromo and N-alkylphthalimido-isatins

The manuscript pertains to the synthesis and in vitro cytotoxic evaluation of a series of N-alkylbromo and N-alkylphthalimido-isatins against four different human cancer cell lines namely Colon: HCT-15; Liver: Hep-2; Lung: A-549 and Leukemia: THP-1 at 10 and 100 μM concentrations. The active compounds based on preliminary studies were evaluated for their IC(50) value against six cell lines viz. Colo-205, HCT-15 (Colon), THP-1 (Leukemia), A-549 (Lung), PC-3 (Prostate) and HeLa (Cervix). The active analogue IS-4 exhibited IC(50) values of 4.57, 10.90, 11.75, 12.40 and 54.20 μM against HeLa, PC-3, HCT-15, THP-1 and Colo-205, respectively.

Synthesis and [4+2] cycloaddition reactions of 4-(N-allyl-N-aryl)amino-1,3-diaza-1,3-butadienes with vinyl-, isopropenyl- and chloroketenes: Entry to novel pyrimidinone/fused pyrimidinone derivatives

Abstract 4-(N-Allyl-N-aryl)amino-1,3-diaza-1,3-butadienes 2, prepared by the treatment of N-arylamino-1,3-diaza-1,3-butadienes 1 with allyl bromide, underwent [4+2] cycloadditions with vinyl/isopropenyl- and accompanied by rearrangements in case of chloroketenes, to yield 5-vinyl/isopropenyl pyrimidinones 5 and 5-methylthio pyrimidinones 19, respectively. The pyrimidinones 5 on refluxing in xylene gave pyrimidoazepines 6, underwent annelation reaction, in refluxing benzene in presence of AlCl3, to yield pyrimidoquinolines 7 and on treatment with DMAD in refluxing toluene, underwent [4+2] cycloaddition accompanied by the elimination of N-allylarylamine functionality to yield quinazolinone 9. Further, the reactions of 5 with PhSH in the presence of AIBN in refluxing benzene followed unusual radical cyclisation involving N-aryl group leading to pyrimidoquinolines 10. The iodocyclisation of pyrimidinones 19 yielded pyrimidothiazines 20.

Synthesis of 5-dienyl pyrimidinones and tandem [1,5] shifts in [4+2] cycloadditions of 1,3-diazabuta-1,3-dienes with butadienylketene

Abstract The reactions of 1-aryl-2-phynyl-4-methylthio-4-secondaryamino / 4- N -allyl- N -aryl amino-1,3-diazabuta-1,3-dienes 1 with butadienylketene leading to a mixture of 5-dienyl pyrimidinones 4 and 5-butenyl pyrimidinones 6 are reported. Tandem [1,5]H and [1,5]SMe shifts are invoked to explain the formation of pyrimidinones 6 .

UNUSUAL 1, 4-METHYLENE TRANSFER FROM A SIMMONS-SMITH REAGENT TO 1,3-DIAZABUTA-1,3-DIENES

Abstract Novel 1,4 methylene transfer from a Simmons-Smith reagent to 1-aryl-4-secondary amino-4-methylthio or methyl-2-phenyl-1,3-diazabuta-1,3-dienes leading to 1-aryl-2-phenyl-4-secondary amino or methyl -imidazoles are described.

Theoretical studies on the conformational preferences of 1,3-diazabuta-1,3-dienes

Abstract Ab initio MO and density functional calculations have been performed to study the conformational preferences for 1,3-diazabuta-1,3-dienes. Complete optimisations using B3LYP/6-31G* level on HNCH–NCH 2 indicate that the conformational preferences are different for the E and Z isomers, E preferring s-cisoid arrangement and Z preferring s-trans arrangement. Natural Bond Order analysis has been carried out on the various conformations of 1,3-diazabuta-1,3-dienes to understand the electron delocalisations and the origin of conformational preferences in these systems. To understand the effect of substituents on conformations, complete optimisations have been carried out with Me, SH, and NH2 substituents at C-2 and C-4 positions. The results indicate that the s-cisoid structure is more stable in most cases and in some cases the s-trans even does not exist. A systematic change in the N1–C2–N3–C4 torsional angle is observed as a function of the electron delocalisation in these systems. The s-cisoid structure tends to be closer to s-cis in the E isomers and such an effect has not been observed in the Z isomers. The preference for the s-trans arrangement and the ϕ values in E - s-cisoid structure are larger in solvent media.

Tandem sigmatropic shifts in [4 + 2] cycloaddition reactions of 1,3-diazabuta-1,3-dienes with butadienylketene: synthesis of pyrimidinone derivatives

The reactions of 4-dialkylamino substituted 1,3-diazabuta-1,3-dienes 1 with butadienylketene 2, are shown to undergo [4 + 2] cycloadditions to yield 5-(buta-1′,3′-dienyl)pyrimidinone 4 and tandem [1,5]H and [1,5]SCH3 shifts are shown to accompany the [4 + 2] cycloaddition reactions of 4-dialkylamino-4-methylthio substituted 1,3-diazabuta-1,3-dienes 5 with 2. The regioselective reactions of N-arylamino-1,3-diazabuta-1,3-dienes 11 and 14 with butadienylketene 2 are reported to yield 5-(buta-1′,3′-dienyl)-2-dialkylaminopyrimidin-4(3H)-one 13 and a mixture of 5-(buta-1′,3′-dienyl)-2-methylthiopyrimidin-4(3H)-one 17, 2-methylthio-5-[1′-(N-phenylamino)but-2′-enyl]pyrimidin-4(3H)-one 19 and 2-methylthio-5-[3′-(N-phenylamino)but-1′-enyl]pyrimidin-4(3H)-one 20, respectively. Tandem [1,5]H, [1,3]NHPh and [1,5]NHPh shifts are involved in the formation of pyrimidinones 19 and 20. The Diels–Alder reactions of the 5-dienylpyrimidinones with dimethyl acetylenedicarboxylate (DMAD) and 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) yielded corresponding cycloadducts.