Dr. Janita Rita Trinita Pinto (original) (raw)
Papers by Dr. Janita Rita Trinita Pinto
Veterinary World, Jun 28, 2024
Background and Aim: Staphylococcus aureus, with its diverse virulence factors and immune response... more Background and Aim: Staphylococcus aureus, with its diverse virulence factors and immune response evasion mechanisms, presents a formidable challenge as an opportunistic pathogen. Developing an effective vaccine against S. aureus has proven elusive despite extensive efforts. Autologous Staphylococcus lysate (ASL) treatment has proven effective in triggering an immune response against bovine mastitis. Peptides that stimulate the immune response can be the subject of further research. The study aimed to use immunoinformatics tools to identify epitopes on S. aureus surface and secretory proteins that can bind to major histocompatibility complex class I (MHC I) and CD8+ T-cells. This method aids in discovering prospective vaccine candidates and elucidating the rationale behind ASL therapy’s efficacy.
Materials and Methods: Proteins were identified using both literature search and the National Center for Biotechnology Information search engine Entrez. Self and non-self peptides, allergenicity predictions, epitope locations, and physicochemical characteristics were determined using sequence alignment, AllerTOP, SVMTriP, and Protein-Sol tools. Hex was employed for simulating the docking interactions between S. aureus proteins and the MHC I + CD8+ T-cells complex. The binding sites of S. aureus proteins were assessed using Computer Atlas of Surface Topography of Proteins (CASTp) while docked with MHC I and CD8+ T-cells.
Results: Nine potential S. aureus peptides and their corresponding epitopes were identified in this study, stimulating cytotoxic T-cell mediated immunity. The peptides were analyzed for similarity with self-antigens and allergenicity. 1d20, 2noj, 1n67, 1nu7, 1amx, and 2b71, non-self and stable, are potential elicitors of the cytotoxic T-cell response. The energy values from docking simulations of peptide-MHC I complexes with the CD8+ and T-cell receptor (TCR) indicate the stability and strength of the formed complexes. These peptides – 2noj, 1d20, 1n67, 2b71, 1nu7, 1yn3, 1amx, 2gi9, and 1edk – demonstrated robust MHC I binding, as evidenced by their low binding energies. Peptide 2gi9 exhibited the lowest energy value, followed by 2noj, 1nu7, 1n67, and 1d20, when docked with MHC I and CD8 + TCR, suggesting a highly stable complex. CASTp analysis indicated substantial binding pockets in the docked complexes, with peptide 1d20 showing the highest values for area and volume, suggesting its potential as an effective elicitor of immunological responses. These peptides – 2noj, 2gi9, 1d20, and 1n67 – stand out for vaccine development and T-cell activation against S. aureus.
Conclusion: This study sheds light on the design and development of S. aureus vaccines, highlighting the significance of employing computational methods in conjunction with experimental verification. The significance of T-cell responses in combating S. aureus infections is emphasized by this study. More experiments are needed to confirm the effectiveness of these vaccine candidates and discover their possible medical uses.
Keywords: autologous Staphylococcus lysate therapy, CD8+ T-cell immunity, computational tools, epitopes, immunoinformatics, immunological responses, major histocompatibility complex class I binding epitopes, molecular docking simulations, Staphylococcus aureus, vaccine development.
European Journal of Obstetrics & Gynecology and Reproductive Biology: X, 2022
Introduction: The worldwide increase in the prevalence of obesity over the years has emerged as a... more Introduction: The worldwide increase in the prevalence of obesity over the years has emerged as a global health concern. The growing rate of obesity in women of child bearing age is particularly a matter of concern. Obesity is considered a risk factor that predisposes an individual to a proinflammatory state through the release of the inflammatory mediators. Recent studies have shown a positive correlation between the severity of inflammation and an increase in adenosine deaminase (ADA) and high sensitivity C- reactive protein (hs-CRP). Obese pregnancy women are at a higher risk for developing inflammation-mediated pregnancy complications like gestational diabetes, preeclampsia, and preterm delivery. Considering the fact that pregnancy, obesity and inflammation are closely linked, this study evaluated the inflammation associated with obesity during pregnancy by estimating changes in ADA and hs-CRP. Materials and methods: The current study aimed to evaluate the levels of inflammation in obese pregnant women compared to non-obese pregnant women by correlating BMI with levels of ADA / hs-CRP. The study also aimed to examine the change in ADA and hs-CRP levels with gestational age (between the 1st and the 3rd trimester) in obese pregnant women as compared to non-obese pregnant women. We also examined whether changes in the levels of ADA correlate with changes in the levels of hs-CRP particularly in obese pregnant women. Blood samples were collected from obese and non-obese pregnant women. ADA activity and hs-CRP levels were estimated by biochemical assays. BMI was evaluated in the 1st trimester and those women with BMI > 30 kg/ m2were considered as obese. Thirty subjects were included in each of the two groups. Results: ADA and hs-CRP levels were significantly higher in obese pregnant women in both the 1st and 3rd trimesters compared to non-obese participants (P value<0.05). Statistically significant higher values of ADA and hs-CRP were seen in obese participants in the 3rd trimester compared to the 1st trimester.A significant linear positive correlation was found between BMI and 3rd trimester ADA, and a linear positive correlation between BMI and hs-CRP both in the 1st and 3rd trimester. The relationship between Δ ADA and Δ hs-CRP was nonsignificant. Conclusions: The observations of this study reveal increased inflammatory responses in obese pregnant women and suggests the importance of ADA and hs-CRP as early indicators of obesity-related complications prevailing thereafter, these markers can be useful for clinical diagnosis of impending maternal and neonatal complications
Journal of South Asian Federation of Obstetrics and Gynaecology, 2021
Introduction: During early life, the neutrophils as components of the innate immune system help t... more Introduction: During early life, the neutrophils as components of the innate immune system help to defend against pathogenic infections. Evaluation of cord blood neutrophil phagocytic index (NPI) has considerable value for understanding innate immune status. Few previous studies have investigated the association of maternal iron levels and neonatal immune status. The association of prenatal factors leading to increased risk of early-onset sepsis (EOS) in neonates is well understood. Neutrophils as components of the innate immune system represent the first line of defense against pathogens and are important especially during early life. Compromised neutrophil phagocytic functions and immune responses have been linked to the development of EOS in neonates. Aims and objectives: (1) To evaluate the phagocytic index of the neutrophils in the cord blood obtained from neonates born to anemic mothers. (2) To evaluate the phagocytic index of the neutrophils in the cord blood obtained from neonates born with risk factors for developing EOS. Materials and methods: To study NPI in neonates born to anemic mothers, 60 mothers and newborn pairs were recruited and subdivided into anemic and nonanemic groups, based on hemoglobin (Hb) levels of maternal blood. To study NPI in cord blood of neonates born with risk factors for EOS, 61 neonates with two or more risk factors for developing sepsis were recruited, along with 48 healthy infants who served as controls. Venous blood samples were collected 1.5 hours ± 20 minutes before the delivery. Five milliliters of cord blood was collected soon after childbirth. Results: The mean NPI values and also the mean gestational age and birth weight were significantly lower (p <0.05) in neonates of anemic mothers. Positive linear correlation (inverse relationship) of r = 0.67 and p <0.05 was observed between maternal Hb and NPI. Neonates with risk of EOS had significantly (p <0.05) lower values of NPI and significantly elevated levels of C-reactive proteins (CRP). Conclusions: There exists a significant association between maternal iron status and lowered phagocytic capacity of neutrophils, suggesting compromised innate immunity in neonates. Lowered NPI in the cord blood of infants born with risk of EOS is suggestive of the compromised immune response, which may add to the risk of developing EOS. Lowered cord blood NPI may mark early neonatal immune deficiency and immune processes in neonates. Further studies on cord blood NPI can lead to identifying NPI as an early predictor of EOS.
Biomedical Research, 2009
Superoxide dismutases (SOD's) are key enzymes which catalyze the dismutation of the O2-free ... more Superoxide dismutases (SOD's) are key enzymes which catalyze the dismutation of the O2-free radical to hydrogen peroxide and oxygen. Hence SOD is an important enzymatic, antioxidant defense in all cells exposed to oxygen. Two different SODs have been described in ...
Biomedicine, 2021
Introduction and Aim: Diabetic foot ulcers are common complications seen in diabetic patients. Tr... more Introduction and Aim: Diabetic foot ulcers are common complications seen in diabetic patients. Treatment of this disabling foot sore remains a challenge to health care professionals. This study aimed at evaluating whether the neutrophils from type 2 diabetic patients with foot ulcers present an impairment of phagocytic index and impairment in respiratory burst. We also aimed at understanding whether the impairment in neutrophil phagocytic activity can be alleviated with short course of standard treatment regime for foot ulcers. Methodology: For this case-controled study, 43 participants with type 2 diabetes (18 with foot ulcers and 25 without foot ulcers) were prospectively recruited along with 18 healthy volunteers. Phagocytic activity of neutrophils and respiratory burst of neutrophils was assessed along with ESR, percentage neutrophil counts before and after 2 weeks of standard treatment for foot ulcers. Results: Neutrophils of type 2 diabetic patients (with and without ...
Journal of South Asian Federation of Obstetrics and Gynaecology
Background: Prenatal stress (PNS) can influence the development of the progeny, which undergoes c... more Background: Prenatal stress (PNS) can influence the development of the progeny, which undergoes complex physiological changes during intrauterine and early postnatal life, thus causing them to experience far-reaching undesirable consequences. Prenatal stress is particularly a challenging issue because, by reacting to the mother's stress through a sequence of biological mechanisms, the fetus is placed under risk of several neurobiological variations that give rise to behavioral and emotional alterations in the offspring. Various studies have been conducted over the last two decades, not only on various stressors that give rise to negative emotions during pregnancy but also on their impact on offspring's mental health during the entire course of their development. Objective: This review aims at discussing various studies on the effect of prenatal stress in animal models and human subjects, and to explore some of the controversies arising in this field. Materials and methods: We searched PubMed and Scopus for English language abstracts published from 1992 to 2021. Search terms were related to prenatal stress, infant or child cognitive and motor development, and developmental psychopathology. Results and conclusion: A vast number of studies have reported negative neurobiological outcomes in the offspring subjected to PNS, although a clear understanding about the underlying biological mechanisms is not available. Methodological challenges do exist in PNS research which has not been successfully overcome. At present, however, there is a definite need to identify, advise, and support pregnant women with some degree of stress with a hope to minimize any adverse consequences in the progeny.
Research Journal of Biotechnology
The pervasive use of organophosphorus compounds as pesticides in recent years has posed a major t... more The pervasive use of organophosphorus compounds as pesticides in recent years has posed a major threat to the population especially to the occupational workers. Once developed as a chemical warfare in the early 1940’s and having been used in World War II as nerve toxic agent, it has gained entry to almost every household worldwide. Malathion, the OP insecticide was first registered for use in 1956 in the United States. The deleterious effects of Malathion are less studied and have been intriguing to the researchers. The current study focused on the immunosuppressing effect of Commercial Grade Malathion (CGM) on normal and infection induced mice assayed by three immunological markers the Adenosine Deaminase (ADA) levels, Hemagglutination titer (HA) and Carbon Clearance index (CCI). A comparative study was made on normal and subcutaneous Staphylococcus aureus (SA) infected mice exposed to 5% LD50 of CGM. The results obtained showed adverse effect on immunological response in mice that...
Biomedical and Pharmacology Journal, 2021
1Department of Biochemistry, RAK College of Medical Sciences,RAK, UAE. 2Department of Pediatrics,... more 1Department of Biochemistry, RAK College of Medical Sciences,RAK, UAE. 2Department of Pediatrics, RAK College of Medical Sciences,RAK, UAE 3Department of Basic Sciences ,RAK University, RAK , UAE. 4Department of Physiology, Manipal Academy of Higher Education,, Manipal, Karnataka, India. 5Department of Biomedical Sciences, College of Medicine, Gulf Medical University, Ajman, UAE. *Corresponding Author E-mail: janitap2010@gmail.com
Superoxide dismutases (SODs) are metalloproteins which bring about dismutation of superoxides and... more Superoxide dismutases (SODs) are metalloproteins which bring about dismutation of superoxides and prevent biological damage of cellular components during oxidative stress. The malarial parasite plasmodium falciparum has a well developed defense system which includes superoxide dismutase, to scavenge free radicals and combat oxidative stress during the erythrocytic stage of its life cycle. Alignment studies of the primary structure of plasmodium falciparum SOD (PfFe-SOD) have shown it to be structurally distinct from human cytosolic copper-zinc SOD1 (Cu-ZnSOD1). This feature makes it a potential target for therapy. A search for new targets as well as drugs is essential due to the phenomenon of drug resistance to chloroquine which is the drug of choice for treatment of malaria. A few potential inhibitors from the library of synthetic molecules have already been studied using recombinant PfFe-SOD by Soulere et al. Three of the fifteen effective lead molecules SP72, SP13 and SP59 show significant inhibition of recombinant PfFe-SOD. However, no attempt was made to investigate whether these lead molecules interact with the host Cu-ZnSOD1. In this study, the lead molecules showing significant inhibition were prepared using Marvin sketch. Cu-ZnSOD1 and PfFe-SOD was docked to these lead molecules and the energy values obtained. The results indicate almost equal affinity of the lead molecules to both, host and parasite, SOD. In conclusion, this study shows that compounds which are found to be quite effective inhibitors of recombinant enzyme in vitro need to be validated by alternate methods since, in the living system, compounds tend to deviate from their in vitro behavior in an unpredicted way. Computational tools such as insilico docking provide the scientist with an alternate base for validation of lead molecules.
Veterinary World, Jun 28, 2024
Background and Aim: Staphylococcus aureus, with its diverse virulence factors and immune response... more Background and Aim: Staphylococcus aureus, with its diverse virulence factors and immune response evasion mechanisms, presents a formidable challenge as an opportunistic pathogen. Developing an effective vaccine against S. aureus has proven elusive despite extensive efforts. Autologous Staphylococcus lysate (ASL) treatment has proven effective in triggering an immune response against bovine mastitis. Peptides that stimulate the immune response can be the subject of further research. The study aimed to use immunoinformatics tools to identify epitopes on S. aureus surface and secretory proteins that can bind to major histocompatibility complex class I (MHC I) and CD8+ T-cells. This method aids in discovering prospective vaccine candidates and elucidating the rationale behind ASL therapy’s efficacy.
Materials and Methods: Proteins were identified using both literature search and the National Center for Biotechnology Information search engine Entrez. Self and non-self peptides, allergenicity predictions, epitope locations, and physicochemical characteristics were determined using sequence alignment, AllerTOP, SVMTriP, and Protein-Sol tools. Hex was employed for simulating the docking interactions between S. aureus proteins and the MHC I + CD8+ T-cells complex. The binding sites of S. aureus proteins were assessed using Computer Atlas of Surface Topography of Proteins (CASTp) while docked with MHC I and CD8+ T-cells.
Results: Nine potential S. aureus peptides and their corresponding epitopes were identified in this study, stimulating cytotoxic T-cell mediated immunity. The peptides were analyzed for similarity with self-antigens and allergenicity. 1d20, 2noj, 1n67, 1nu7, 1amx, and 2b71, non-self and stable, are potential elicitors of the cytotoxic T-cell response. The energy values from docking simulations of peptide-MHC I complexes with the CD8+ and T-cell receptor (TCR) indicate the stability and strength of the formed complexes. These peptides – 2noj, 1d20, 1n67, 2b71, 1nu7, 1yn3, 1amx, 2gi9, and 1edk – demonstrated robust MHC I binding, as evidenced by their low binding energies. Peptide 2gi9 exhibited the lowest energy value, followed by 2noj, 1nu7, 1n67, and 1d20, when docked with MHC I and CD8 + TCR, suggesting a highly stable complex. CASTp analysis indicated substantial binding pockets in the docked complexes, with peptide 1d20 showing the highest values for area and volume, suggesting its potential as an effective elicitor of immunological responses. These peptides – 2noj, 2gi9, 1d20, and 1n67 – stand out for vaccine development and T-cell activation against S. aureus.
Conclusion: This study sheds light on the design and development of S. aureus vaccines, highlighting the significance of employing computational methods in conjunction with experimental verification. The significance of T-cell responses in combating S. aureus infections is emphasized by this study. More experiments are needed to confirm the effectiveness of these vaccine candidates and discover their possible medical uses.
Keywords: autologous Staphylococcus lysate therapy, CD8+ T-cell immunity, computational tools, epitopes, immunoinformatics, immunological responses, major histocompatibility complex class I binding epitopes, molecular docking simulations, Staphylococcus aureus, vaccine development.
European Journal of Obstetrics & Gynecology and Reproductive Biology: X, 2022
Introduction: The worldwide increase in the prevalence of obesity over the years has emerged as a... more Introduction: The worldwide increase in the prevalence of obesity over the years has emerged as a global health concern. The growing rate of obesity in women of child bearing age is particularly a matter of concern. Obesity is considered a risk factor that predisposes an individual to a proinflammatory state through the release of the inflammatory mediators. Recent studies have shown a positive correlation between the severity of inflammation and an increase in adenosine deaminase (ADA) and high sensitivity C- reactive protein (hs-CRP). Obese pregnancy women are at a higher risk for developing inflammation-mediated pregnancy complications like gestational diabetes, preeclampsia, and preterm delivery. Considering the fact that pregnancy, obesity and inflammation are closely linked, this study evaluated the inflammation associated with obesity during pregnancy by estimating changes in ADA and hs-CRP. Materials and methods: The current study aimed to evaluate the levels of inflammation in obese pregnant women compared to non-obese pregnant women by correlating BMI with levels of ADA / hs-CRP. The study also aimed to examine the change in ADA and hs-CRP levels with gestational age (between the 1st and the 3rd trimester) in obese pregnant women as compared to non-obese pregnant women. We also examined whether changes in the levels of ADA correlate with changes in the levels of hs-CRP particularly in obese pregnant women. Blood samples were collected from obese and non-obese pregnant women. ADA activity and hs-CRP levels were estimated by biochemical assays. BMI was evaluated in the 1st trimester and those women with BMI &amp;gt; 30 kg/ m2were considered as obese. Thirty subjects were included in each of the two groups. Results: ADA and hs-CRP levels were significantly higher in obese pregnant women in both the 1st and 3rd trimesters compared to non-obese participants (P value&amp;lt;0.05). Statistically significant higher values of ADA and hs-CRP were seen in obese participants in the 3rd trimester compared to the 1st trimester.A significant linear positive correlation was found between BMI and 3rd trimester ADA, and a linear positive correlation between BMI and hs-CRP both in the 1st and 3rd trimester. The relationship between Δ ADA and Δ hs-CRP was nonsignificant. Conclusions: The observations of this study reveal increased inflammatory responses in obese pregnant women and suggests the importance of ADA and hs-CRP as early indicators of obesity-related complications prevailing thereafter, these markers can be useful for clinical diagnosis of impending maternal and neonatal complications
Journal of South Asian Federation of Obstetrics and Gynaecology, 2021
Introduction: During early life, the neutrophils as components of the innate immune system help t... more Introduction: During early life, the neutrophils as components of the innate immune system help to defend against pathogenic infections. Evaluation of cord blood neutrophil phagocytic index (NPI) has considerable value for understanding innate immune status. Few previous studies have investigated the association of maternal iron levels and neonatal immune status. The association of prenatal factors leading to increased risk of early-onset sepsis (EOS) in neonates is well understood. Neutrophils as components of the innate immune system represent the first line of defense against pathogens and are important especially during early life. Compromised neutrophil phagocytic functions and immune responses have been linked to the development of EOS in neonates. Aims and objectives: (1) To evaluate the phagocytic index of the neutrophils in the cord blood obtained from neonates born to anemic mothers. (2) To evaluate the phagocytic index of the neutrophils in the cord blood obtained from neonates born with risk factors for developing EOS. Materials and methods: To study NPI in neonates born to anemic mothers, 60 mothers and newborn pairs were recruited and subdivided into anemic and nonanemic groups, based on hemoglobin (Hb) levels of maternal blood. To study NPI in cord blood of neonates born with risk factors for EOS, 61 neonates with two or more risk factors for developing sepsis were recruited, along with 48 healthy infants who served as controls. Venous blood samples were collected 1.5 hours ± 20 minutes before the delivery. Five milliliters of cord blood was collected soon after childbirth. Results: The mean NPI values and also the mean gestational age and birth weight were significantly lower (p <0.05) in neonates of anemic mothers. Positive linear correlation (inverse relationship) of r = 0.67 and p <0.05 was observed between maternal Hb and NPI. Neonates with risk of EOS had significantly (p <0.05) lower values of NPI and significantly elevated levels of C-reactive proteins (CRP). Conclusions: There exists a significant association between maternal iron status and lowered phagocytic capacity of neutrophils, suggesting compromised innate immunity in neonates. Lowered NPI in the cord blood of infants born with risk of EOS is suggestive of the compromised immune response, which may add to the risk of developing EOS. Lowered cord blood NPI may mark early neonatal immune deficiency and immune processes in neonates. Further studies on cord blood NPI can lead to identifying NPI as an early predictor of EOS.
Biomedical Research, 2009
Superoxide dismutases (SOD's) are key enzymes which catalyze the dismutation of the O2-free ... more Superoxide dismutases (SOD's) are key enzymes which catalyze the dismutation of the O2-free radical to hydrogen peroxide and oxygen. Hence SOD is an important enzymatic, antioxidant defense in all cells exposed to oxygen. Two different SODs have been described in ...
Biomedicine, 2021
Introduction and Aim: Diabetic foot ulcers are common complications seen in diabetic patients. Tr... more Introduction and Aim: Diabetic foot ulcers are common complications seen in diabetic patients. Treatment of this disabling foot sore remains a challenge to health care professionals. This study aimed at evaluating whether the neutrophils from type 2 diabetic patients with foot ulcers present an impairment of phagocytic index and impairment in respiratory burst. We also aimed at understanding whether the impairment in neutrophil phagocytic activity can be alleviated with short course of standard treatment regime for foot ulcers. Methodology: For this case-controled study, 43 participants with type 2 diabetes (18 with foot ulcers and 25 without foot ulcers) were prospectively recruited along with 18 healthy volunteers. Phagocytic activity of neutrophils and respiratory burst of neutrophils was assessed along with ESR, percentage neutrophil counts before and after 2 weeks of standard treatment for foot ulcers. Results: Neutrophils of type 2 diabetic patients (with and without ...
Journal of South Asian Federation of Obstetrics and Gynaecology
Background: Prenatal stress (PNS) can influence the development of the progeny, which undergoes c... more Background: Prenatal stress (PNS) can influence the development of the progeny, which undergoes complex physiological changes during intrauterine and early postnatal life, thus causing them to experience far-reaching undesirable consequences. Prenatal stress is particularly a challenging issue because, by reacting to the mother's stress through a sequence of biological mechanisms, the fetus is placed under risk of several neurobiological variations that give rise to behavioral and emotional alterations in the offspring. Various studies have been conducted over the last two decades, not only on various stressors that give rise to negative emotions during pregnancy but also on their impact on offspring's mental health during the entire course of their development. Objective: This review aims at discussing various studies on the effect of prenatal stress in animal models and human subjects, and to explore some of the controversies arising in this field. Materials and methods: We searched PubMed and Scopus for English language abstracts published from 1992 to 2021. Search terms were related to prenatal stress, infant or child cognitive and motor development, and developmental psychopathology. Results and conclusion: A vast number of studies have reported negative neurobiological outcomes in the offspring subjected to PNS, although a clear understanding about the underlying biological mechanisms is not available. Methodological challenges do exist in PNS research which has not been successfully overcome. At present, however, there is a definite need to identify, advise, and support pregnant women with some degree of stress with a hope to minimize any adverse consequences in the progeny.
Research Journal of Biotechnology
The pervasive use of organophosphorus compounds as pesticides in recent years has posed a major t... more The pervasive use of organophosphorus compounds as pesticides in recent years has posed a major threat to the population especially to the occupational workers. Once developed as a chemical warfare in the early 1940’s and having been used in World War II as nerve toxic agent, it has gained entry to almost every household worldwide. Malathion, the OP insecticide was first registered for use in 1956 in the United States. The deleterious effects of Malathion are less studied and have been intriguing to the researchers. The current study focused on the immunosuppressing effect of Commercial Grade Malathion (CGM) on normal and infection induced mice assayed by three immunological markers the Adenosine Deaminase (ADA) levels, Hemagglutination titer (HA) and Carbon Clearance index (CCI). A comparative study was made on normal and subcutaneous Staphylococcus aureus (SA) infected mice exposed to 5% LD50 of CGM. The results obtained showed adverse effect on immunological response in mice that...
Biomedical and Pharmacology Journal, 2021
1Department of Biochemistry, RAK College of Medical Sciences,RAK, UAE. 2Department of Pediatrics,... more 1Department of Biochemistry, RAK College of Medical Sciences,RAK, UAE. 2Department of Pediatrics, RAK College of Medical Sciences,RAK, UAE 3Department of Basic Sciences ,RAK University, RAK , UAE. 4Department of Physiology, Manipal Academy of Higher Education,, Manipal, Karnataka, India. 5Department of Biomedical Sciences, College of Medicine, Gulf Medical University, Ajman, UAE. *Corresponding Author E-mail: janitap2010@gmail.com
Superoxide dismutases (SODs) are metalloproteins which bring about dismutation of superoxides and... more Superoxide dismutases (SODs) are metalloproteins which bring about dismutation of superoxides and prevent biological damage of cellular components during oxidative stress. The malarial parasite plasmodium falciparum has a well developed defense system which includes superoxide dismutase, to scavenge free radicals and combat oxidative stress during the erythrocytic stage of its life cycle. Alignment studies of the primary structure of plasmodium falciparum SOD (PfFe-SOD) have shown it to be structurally distinct from human cytosolic copper-zinc SOD1 (Cu-ZnSOD1). This feature makes it a potential target for therapy. A search for new targets as well as drugs is essential due to the phenomenon of drug resistance to chloroquine which is the drug of choice for treatment of malaria. A few potential inhibitors from the library of synthetic molecules have already been studied using recombinant PfFe-SOD by Soulere et al. Three of the fifteen effective lead molecules SP72, SP13 and SP59 show significant inhibition of recombinant PfFe-SOD. However, no attempt was made to investigate whether these lead molecules interact with the host Cu-ZnSOD1. In this study, the lead molecules showing significant inhibition were prepared using Marvin sketch. Cu-ZnSOD1 and PfFe-SOD was docked to these lead molecules and the energy values obtained. The results indicate almost equal affinity of the lead molecules to both, host and parasite, SOD. In conclusion, this study shows that compounds which are found to be quite effective inhibitors of recombinant enzyme in vitro need to be validated by alternate methods since, in the living system, compounds tend to deviate from their in vitro behavior in an unpredicted way. Computational tools such as insilico docking provide the scientist with an alternate base for validation of lead molecules.