Drug screening using shape-based virtual screening and in vitro experimental models of cutaneous Leishmaniasis

Cutaneous leishmaniasis (CL) is one of the most disregarded tropical neglected disease with the occurrence of self-limiting ulcers and triggering mucosal damage and stigmatizing scars, leading to huge public health problems and social negative impacts. Pentavalent antimonials are the first-line drug for CL treatment for over 70 years and present several drawbacks in terms of safety and efficacy. Thus, there is an urgent need to search for non-invasive, non-toxic and potent drug candidates for CL. In this sense, we have implemented a shape-based virtual screening approach and identified a set of 32 hit compounds. In vitro phenotypic screenings were conducted using these hit compounds to check their potential leishmanicidal effect towards Leishmania amazonensis (L. amazonensis). Two (Cp1 and Cp2) out of the 32 compounds revealed promising antiparasitic activities, exhibiting considerable potency against intracellular amastigotes present in peritoneal macrophages (IC₅₀ values of 9.35 and 7.25 μm, respectively). Also, a sterile cidality profile was reached at 20 μm after 48 h of incubation, besides a reasonable selectivity (≈8), quite similarly to pentamidine, a diamidine still in use clinically for leishmaniasis. Cp1 with an oxazolo[4,5-b]pyridine scaffold and Cp2 with benzimidazole scaffold could be developed by lead optimization studies to enhance their leishmanicidal potency

Implementation of TCP Congestion Control mechanism for Wireless Networks using TCP Reserved Field and Signal to Noise Ratio (SNR)

TCP is the most popular and widely used network transmission protocol. All most 90% of the Internet connections make use of TCP for communication. TCP is reliable for wired networks and it considers all packet timeouts in wired networks as due to network congestion and not because of bit errors. However, TCP suffers from performance degradation over error-prone wireless links, as it has no technique to distinguish error deficits from congestion deficits, with networking becoming more divergent, with wired and wireless topologies. It considers all packet deficits are due to congestion and subsequently reduces the packet burst transmission, at the same time decreasing the network throughput. In this paper a new TCP congestion control mechanism is proposed that is suitable and applicable for wireless and also for wired networks and is capable of distinguishing congestion deficits from error deficits. The proposed technique uses the reserved field of the TCP header to indicate whether the connection established is over a wired or a wireless link. Further, the proposed technique influences the usage of Signal to Noise Ratio (SNR) to discover the reliability of the link and determine whether to decrease the packet burst or retransmit the timed-out packet. Investigations performed, revealed that the proposed mechanism confirmed to function amend in circumstances where timeouts were due to error and not due to congestion. Further, the future work can be enhanced upon the proposed mechanism so that it can leverage Cyclic Redundancy Check(CRC) and Header Error Check(HEC) errors so that it can be properly determined the reason for initializing transmission timeouts in wireless networks.

Ripple Reduction Using Seven-Level Shunt Active Power Filter for High-Power Drives and Non-Linear Load System

ABSTRACT: This Paper proposes the high-power non-linear loads and high-power adjustable-speed motor drives, such as mainly used in electric novel ships, the shunt active power filter is proposed here to reduce the harmonic contents in source voltage and source currents of harmonic polluted three phase system supplying a Non-linear load and drives. The Shunt active filter is designed with Seven level cascaded H-bridge inverter. To handle the large compensation currents and provide better thermal management, two or more paralleled semiconductor switching devices can be used. In this paper two active filter inverters are connected with tapped reactors to share the compensation currents. Based on the joint redundant state selection strategy, a current balancing algorithm is proposed to keep the reactor magnetizing current to a minimum. The active filter topology can produce seven voltage levels. The harmonic filter reduces the harmonic contents in source currents as well as the source voltage multilevel shunt active filter does not require an interfacing transformer to connect it with the high power system. This is shown through simulation that the proposed active filter can achieve high overall system performance

Spectrophotometric determination of Isoproturon and Metoxuron in technical and formulation grade samples using citric acid-acetic anhydride reagent

196-200<span style="font-size:11.0pt;line-height:115%; font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "dejavu="" sans";mso-hansi-theme-font:minor-latin;mso-bidi-font-family:mangal;="" mso-bidi-theme-font:minor-bidi;color:#00000a;mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">A spectrophotometric method for the determination of Isoproturon and Metoxuron in technical and formulation grade samples based on the reaction with citric acid-acetic anhydride reagent has been developed. The absorption maxima of the coloured compounds so formed are 408 and 409 nm and the molar absorptivities are 1.69 x 102 and 1.13 x 102 L mol-1 cm-1 respectively. The reaction variables have been optimized and the reaction mechanism is discussed. The method is simple, convenient and successfully applied for the determination of Isoproturon and Metoxuron in technical and formulation grade samples. The percent relative standard deviation is found to be in the range 0.6-1.55 for Isoproturon and 1.24-1.90 for Metoxuron.</span

Yb(OTf)(3) mediated MCR: a new and regioselective approach towards polysubstituted pyrroles of pharmacological interest

A regioselective synthesis of 1,2,3,4-tetrasubstituted pyrroles has been achieved via Yb(OTf)-mediated 3-component reaction of amines, a 1,3-diketone and phenacyl bromide in a single pot. Yb(OTf) was identified as a reusable catalyst and a number of pyrrole derivatives were prepared by using this strategy. Single crystal X-ray diffraction study of a representative compound confirmed the substitution pattern on the central pyrrole ring. The crystal structure analysis of the same compound indicated the presence of a sheet-like molecular arrangement along the bc-plane present in the molecule. A possible mechanism for the regioselective formation of 1,2,3,4-tetrasubstituted pyrrole rings is discussed. A number of compounds synthesized showed PDE4 inhibitory properties when tested in vitro and two of them were identified as inhibitors of further interest

Facile assembly of two 6-membered fused N-heterocyclic rings: a rapid access to novel small molecules via Cu-mediated reaction

A rapid, versatile and one-pot Cu-mediated domino reaction has been developed for facile assembly of two six membered fused N-heterocyclic rings leading to novel small molecules as potential inhibitors of PDE4

Novel thieno[2,3-d]pyrimidines: Their design, synthesis, crystal structure analysis and pharmacological evaluation

Novel thieno[2,3-d]pyrimidines containing a cyclohexane ring fused with a six- or five-membered heterocyclic moiety along with a benzylic nitrile were designed as potential inhibitors of PDE4. Expeditious synthesis of these compounds was carried out via a multi-step sequence consisting of a few key steps such as Gewald reaction, Dieckmann type cyclisation and Krapcho decarboxylation. This newly developed strategy involved construction of the thienopyrimidine ring followed by the cyclohexanone moiety and subsequently the fused heterocyclic ring. A number of thieno[2,3-d]pyrimidine based derivatives were synthesized using this method some of which showed promising PDE4B inhibitory properties. One of them was tested for PDE4D inhibition in vitro and dose dependent inhibition of TNF-α. A few selected molecules were docked into the PE4B protein the results of which showed good overall correlations to their observed PDE4B inhibitory properties in vitro. The crystal structure analysis of representative compounds along with hydrogen bonding patterns and molecular arrangement present within the molecule is described