Aminoquinoline

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Diwan S. Rawat - One of the best experts on this subject based on the ideXlab platform.

Prem M S Chauhan - One of the best experts on this subject based on the ideXlab platform.

  • Synthesis of new 4-Aminoquinolines and quinoline-acridine hybrids as antimalarial agents.
    Bioorganic & Medicinal Chemistry Letters, 2010
    Co-Authors: Ashok Kumar, Kumkum Srivastava, S. Raja Kumar, Surendra Puri, Prem M S Chauhan
    Abstract:

    Abstract Despite emergence of resistance to CQ and other 4-Aminoquinoline drugs in most of the endemic regions, research findings provide considerable support that there is still significant potential to discover new affordable, safe, and efficacious 4-Aminoquinoline antimalarials. In present study, new side chain modified 4-Aminoquinoline derivatives and quinoline–acridine hybrids were synthesized and evaluated in vitro against NF 54 strain of Plasmodium falciparum. Among the evaluated compounds, compound 17 (MIC = 0.125 μg/mL) was equipotent to standard drug CQ (MIC = 0.125 μg/mL) and compound 21 (MIC = 0.031 μg/mL) was four times more potent than CQ. Compound 17 showed the curative response to all the treated swiss mice infected with CQ-resistant N-67 strain of Plasmodium yoelii at the doses 50 mg/kg and 25 mg/kg for four days by intraperitoneal route and was found to be orally active at the dose of 100 mg/kg for four days. The promising antimalarial potency of compound 17 highlights the significance of exploring the privileged 4-Aminoquinoline class for new antimalarials.

  • synthesis of novel thiourea thiazolidinedione and thioparabanic acid derivatives of 4 Aminoquinoline as potent antimalarials
    Bioorganic & Medicinal Chemistry Letters, 2009
    Co-Authors: Naresh Sunduru, Kumkum Srivastava, J K Saxena, Sundaresan Rajakumar, Sunil K Puri, Prem M S Chauhan
    Abstract:

    In search of new 4-Aminoquinolines which are not recognized by CQR mechanism, thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-Aminoquinoline were synthesized and screened for their antimalarial activity. Thiourea derivative 3 found to be the most active against CQ sensitive strain 3D7 of P. falciparum in an in vitro model with an IC50 of 6.07 ng/mL and also showed in vivo suppression of 99.27% on day 4 against CQ resistant strain N-67 of P. yoelii. Malaria is a devastating disease caused by four species of genus plasmodium which afflicts more than 40% of the world population, causing an estimated mortality of 1.5-2.7 million people annually. 1 The current epidemic is fueled about the parasite Plasmodium falciparum, responsible for the most deadly cases of malaria and its resistance to the antimalarial drugs. Chloroquine (CQ) has historically been mainstay of malaria treatment, particularly with P. falciparum in pregnant women and children under the age of five. 2 It acts by binding to heme molecules released from the hemoglobin that is digested by malaria parasites as they grow within their host red blood cells. This binding interferes with the process by which heme is normally incorporated into inert crystals (β-hematin) and detoxified, thereby accumulation of toxic levels of heme leads to the death of parasite.

  • synthesis of novel thiourea thiazolidinedione and thioparabanic acid derivatives of 4 Aminoquinoline as potent antimalarials
    Bioorganic & Medicinal Chemistry Letters, 2009
    Co-Authors: Naresh Sunduru, Kumkum Srivastava, J K Saxena, Sundaresan Rajakumar, Sunil K Puri, Prem M S Chauhan
    Abstract:

    Abstract In search of new 4-Aminoquinolines which are not recognized by CQR mechanism, thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-Aminoquinoline were synthesized and screened for their antimalarial activities. Thiourea derivative 3 found to be the most active against CQ sensitive strain 3D7 of Plasmodium falciparum in an in vitro model with an IC50 of 6.07 ng/mL and also showed an in vivo suppression of 99.27% on day 4 against CQ resistant strain N-67 of Plasmodium yoelii.

Sunny Manohar - One of the best experts on this subject based on the ideXlab platform.

Naresh Sunduru - One of the best experts on this subject based on the ideXlab platform.

  • synthesis of novel thiourea thiazolidinedione and thioparabanic acid derivatives of 4 Aminoquinoline as potent antimalarials
    Bioorganic & Medicinal Chemistry Letters, 2009
    Co-Authors: Naresh Sunduru, Kumkum Srivastava, J K Saxena, Sundaresan Rajakumar, Sunil K Puri, Prem M S Chauhan
    Abstract:

    In search of new 4-Aminoquinolines which are not recognized by CQR mechanism, thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-Aminoquinoline were synthesized and screened for their antimalarial activity. Thiourea derivative 3 found to be the most active against CQ sensitive strain 3D7 of P. falciparum in an in vitro model with an IC50 of 6.07 ng/mL and also showed in vivo suppression of 99.27% on day 4 against CQ resistant strain N-67 of P. yoelii. Malaria is a devastating disease caused by four species of genus plasmodium which afflicts more than 40% of the world population, causing an estimated mortality of 1.5-2.7 million people annually. 1 The current epidemic is fueled about the parasite Plasmodium falciparum, responsible for the most deadly cases of malaria and its resistance to the antimalarial drugs. Chloroquine (CQ) has historically been mainstay of malaria treatment, particularly with P. falciparum in pregnant women and children under the age of five. 2 It acts by binding to heme molecules released from the hemoglobin that is digested by malaria parasites as they grow within their host red blood cells. This binding interferes with the process by which heme is normally incorporated into inert crystals (β-hematin) and detoxified, thereby accumulation of toxic levels of heme leads to the death of parasite.

  • synthesis of novel thiourea thiazolidinedione and thioparabanic acid derivatives of 4 Aminoquinoline as potent antimalarials
    Bioorganic & Medicinal Chemistry Letters, 2009
    Co-Authors: Naresh Sunduru, Kumkum Srivastava, J K Saxena, Sundaresan Rajakumar, Sunil K Puri, Prem M S Chauhan
    Abstract:

    Abstract In search of new 4-Aminoquinolines which are not recognized by CQR mechanism, thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-Aminoquinoline were synthesized and screened for their antimalarial activities. Thiourea derivative 3 found to be the most active against CQ sensitive strain 3D7 of Plasmodium falciparum in an in vitro model with an IC50 of 6.07 ng/mL and also showed an in vivo suppression of 99.27% on day 4 against CQ resistant strain N-67 of Plasmodium yoelii.

Sunil K Puri - One of the best experts on this subject based on the ideXlab platform.

  • antiplasmodial activity of new 4 Aminoquinoline derivatives against chloroquine resistant strain
    Bioorganic & Medicinal Chemistry, 2014
    Co-Authors: Manish Sinha, Kumkum Srivastava, Vasantha Rao Dola, Pooja Agarwal, Sunil K Puri, Seturam Bandachar Katti
    Abstract:

    Abstract Emergence and spread of multidrug resistant strains of Plasmodium falciparum has severely limited the antimalarial chemotherapeutic options. In order to overcome the obstacle, a set of new side-chain modified 4-Aminoquinolines were synthesized and screened against chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of P. falciparum . The key feature of the designed molecules is the use of methylpiperazine linked α, β 3 - and γ-amino acids to generate novel side chain modified 4-Aminoquinoline analogues. Among the evaluated compounds, 20c and 30 were found more potent than CQ against K1 and displayed a four-fold and a three-fold higher activity respectively, with a good selectivity index (SI = 5846 and 11,350). All synthesized compounds had resistance index between 1.06 and >14.13 as against 47.2 for chloroquine. Biophysical studies suggested that this series of compounds act on heme polymerization target.

  • synthesis of novel thiourea thiazolidinedione and thioparabanic acid derivatives of 4 Aminoquinoline as potent antimalarials
    Bioorganic & Medicinal Chemistry Letters, 2009
    Co-Authors: Naresh Sunduru, Kumkum Srivastava, J K Saxena, Sundaresan Rajakumar, Sunil K Puri, Prem M S Chauhan
    Abstract:

    In search of new 4-Aminoquinolines which are not recognized by CQR mechanism, thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-Aminoquinoline were synthesized and screened for their antimalarial activity. Thiourea derivative 3 found to be the most active against CQ sensitive strain 3D7 of P. falciparum in an in vitro model with an IC50 of 6.07 ng/mL and also showed in vivo suppression of 99.27% on day 4 against CQ resistant strain N-67 of P. yoelii. Malaria is a devastating disease caused by four species of genus plasmodium which afflicts more than 40% of the world population, causing an estimated mortality of 1.5-2.7 million people annually. 1 The current epidemic is fueled about the parasite Plasmodium falciparum, responsible for the most deadly cases of malaria and its resistance to the antimalarial drugs. Chloroquine (CQ) has historically been mainstay of malaria treatment, particularly with P. falciparum in pregnant women and children under the age of five. 2 It acts by binding to heme molecules released from the hemoglobin that is digested by malaria parasites as they grow within their host red blood cells. This binding interferes with the process by which heme is normally incorporated into inert crystals (β-hematin) and detoxified, thereby accumulation of toxic levels of heme leads to the death of parasite.

  • synthesis of novel thiourea thiazolidinedione and thioparabanic acid derivatives of 4 Aminoquinoline as potent antimalarials
    Bioorganic & Medicinal Chemistry Letters, 2009
    Co-Authors: Naresh Sunduru, Kumkum Srivastava, J K Saxena, Sundaresan Rajakumar, Sunil K Puri, Prem M S Chauhan
    Abstract:

    Abstract In search of new 4-Aminoquinolines which are not recognized by CQR mechanism, thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-Aminoquinoline were synthesized and screened for their antimalarial activities. Thiourea derivative 3 found to be the most active against CQ sensitive strain 3D7 of Plasmodium falciparum in an in vitro model with an IC50 of 6.07 ng/mL and also showed an in vivo suppression of 99.27% on day 4 against CQ resistant strain N-67 of Plasmodium yoelii.

  • Synthesis and Antimalarial Activity of Novel Side Chain Modified Antimalarial Agents Derived from 4-Aminoquinoline
    Medicinal Chemistry, 2008
    Co-Authors: V. Raja Solomon, Kumkum Srivastava, M. Smilkstein, Sundaresan Rajakumar, Sunil K Puri, Seturam Bandachar Katti
    Abstract:

    Malaria is one of the foremost public health problems in developing countries affecting nearly 40% of the global population. Apart from this, the past two decades emergence of drug resistance has severely limited the choice of available antimalarial drugs. Furthermore, the general trend emerging from the SAR-studies is that chloroquine resistance does not involve any change to the target of this class of drugs but involves compound specific efflux mechanism. Based on this premise a number of groups have developed short chain analogues of 4-Aminoquinoline, which are active against CQ-resistant strains of P. falciparum in in vitro studies. However, these derivatives undergo biotransformation (dealklyation) significantly affecting lipid solubility of the drug. In view of this background information, we thought that it would be interesting to study the effect of additional lipophilicity and cationic charge at the lateral side chain of 4- Aminoquinoline. This prompted us to explore the cationic amino acid conjugates namely, lysine and ornithine of 4- Aminoquinoline with a view to achieve improved antimalarial activity and to the best of our knowledge such amino acid conjugates have not been hitherto reported in the literature in the case of 4-Aminoquinolines. In the present study, a new series of side-chain modified 4-Aminoquinolines have been synthesized and found active against both susceptible and multidrug resistant strains of P. falciparum in vitro and P. yoelli in vivo. The seminal finding of the present study is that a new series of compounds having significantly more activity against CQ resistant parasites has been identified.