Molecular Modeling and 3D-QSAR Studies in 2-Aziridinyl-and 2,3-Bis(Aziridinyl)-1,4-Naphthoquinonyl Sulfonate and Acylate Derivatives as Potential Antimalarial Agents

Abstract

Malaria is still continuing to be one of the most dreadful diseases of the tropical countries particularly due to the development of resistance to the existing antimalarials. From observed, antimalarial activity of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives acting through redox cycling mechanism, molecular modeling and three dimensional-quantitative structure activity relationship (3D-QSAR) studies have been carried out on a set of 63 compounds to identify important pharmacophors. Among several 3D-QSAR models generated, three models with correlation coefficient r > 0.82, match > 0.60 and chance = 0.00 have shown two common biophoric sites: one being the oxygen atom at position 1 of the naphthoquinone ring in terms of π-population, charge and electron donating ability while the second being the center of the phenyl ring in terms of its 6π-electrons. In addition to these sites, the models also share two common secondary sites: one positively contributing H-acceptor site while the second site contributing negatively in terms of steric refractivity. All these models showed good agreement between the experimental, calculated and predicted antimalarial activities.     

ON AVOIDANCE ACTIVITIES IN FISHERY ENFORCEMENT MODELS

Compliance and enforcement in fisheries are important issues from an economic point of view since management measures are useless without a certain level of enforcement. These conclusions come from the well‐established theoretical literature on compliance and enforcement problems within fisheries and a common result is that, it is efficient to set fines as high as possible and monitoring as low as possible, when fines are costless and offenders are risk neutral. However, this result is sensitive to the assumption that fishermen cannot engage in avoidance activities, e.g., activities to reduce the likelihood of being detected when noncomplying. The paper presents a model of fisheries that allows the fishermen to engage in avoidance activities. The conclusions from the model are that, under certain circumstances, fines are costly transfers to society since they not only have a direct positive effect on the level of deterrence, but also an indirect negative effect in the form of increased avoidance activities to reduce the probability of detection. The paper contributes to the literature on avoidance activities by introducing the externality from the illegal behavior as an endogenous effect on other offenders. For an externality, that has an exogenous effect on other actors, Malik shows that fines are only costly transfers for conditional deterrence (when one actor is deterred while another actor is not). For fisheries, we show that fines are also costly transfers under no deterrence (when no agents are deterred).     

Molecular modeling and 3D-QSAR studies in 2-aziridinyl-and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives as potential antimalarial agents

Malaria is still continuing to be one of the most dreadful diseases of the tropical countries particularly due to the development of resistance to the existing antimalarials. From observed, antimalarial activity of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives acting through redox cycling mechanism, molecular modeling and three dimensional-quantitative structure activity relationship (3D-QSAR) studies have been carried out on a set of 63 compounds to identify important pharmacophors. Among several 3D-QSAR models generated, three models with correlation coefficient r > 0.82, match > 0.60 and chance = 0.00 have shown two common biophoric sites: one being the oxygen atom at position 1 of the naphthoquinone ring in terms of pi-population, charge and electron donating ability while the second being the center of the phenyl ring in terms of its 6pi-electrons. In addition to these sites, the models also share two common secondary sites: one positively contributing H-acceptor site while the second site contributing negatively in terms of steric refractivity. All these models showed good agreement between the experimental, calculated and predicted antimalarial activities.     

Growth and Thermal,Electrical, Structural Characterization of Mixed Hydrated Single Crystal

Mixed single crystal was made by mixing saturated aqueous solutions of NiSO₄ · 6H₂O and CuSO₄ · 5H₂O by volume (80:20) and the mixture was kept to form the crystals at room temperature by slow evaporation process. After some days, big pieces of greenish blue, dark colored crystals were grown. To determine the weight of NiSO₄ · 6H₂O and CuSO₄ · 5H₂O in the crystal, Ni-DMG complexiometrical and EDTA gravimetrical analysis was done respectively. From this analysis it was concluded that 5.8 molecules of water of crystallization is present in the mixed single crystal. The crystals were characterized by UV-Visible, FTIR and single crystal X-ray diffraction studies. From single crystal XRD lattice parameters have been calculated. All these structural analysis confirms formation of new single crystal. Further, DTA-TGA, dc electrical conductivity and dielectric constant studies were done from the room temperature to 400 °C.From DTA studies it was observed that 5.8 molecules of water of crystallization get dehydrated in four major steps at temperature 115 °C, 150 °C, 240 °C and 325 °C respectively corresponding to the detachment of 1 mole, 3 moles, 1 mole and 0.8 mole of water of crystallization. DC electrical conductivity and dielectric constant studies also show close agreement to the dehydration steps. The observed peaks in the conductivity verses temperature graph have been explained on the basis of release of water molecules and subsequent dissociation of these released water molecules into H⁺ and OH⁻ ions.