Rama Pati Tripathi

Publications of Rama Pati Tripathi

• Synthesis, molecular modeling and bio-evaluation of cycloalkyl fused 2-aminopyrimidines as antitubercular and antidiabetic agents.

  Authors: Nimisha Singh, Sarvesh Kumar Pandey, Namrata Anand, Richa Dwivedi, Shyam Singh, Sudhir Kumar Sinha, Vinita Chaturvedi, Natasa Jaiswal, Arvind Kumar Srivastava, Priyanka Shah, M Imran Siddiqui, Rama Pati Tripathi

  Bioorganic & medicinal chemistry letters. 08/2011; 21(15):4404-8.

  An economical and efficient one step synthesis of a series of 8-(arylidene)-4-(aryl)-5,6,7,8-tetrahydro-quinazolin-2-ylamines andAn economical and efficient one step synthesis of a series of 8-(arylidene)-4-(aryl)-5,6,7,8-tetrahydro-quinazolin-2-ylamines and 9-(arylidene)-4-(aryl)-6,7,8,9-tetrahydro-5H-cycloheptapyrimidin-2-ylamines by the reaction of bis-benzylidene cycloalkanones and guanidine hydrochloride in presence of NaH has been developed. All the synthesized compounds were evaluated against Mycobacterium tuberculosis H(37)Rv strain and the α-glucosidase and glycogen phosphorylase enzymes. Few of the compounds have shown interesting in vitro activity with MIC up to 3.12 μg/mL against M. tuberculosis and very good inhibition of α-glucosidase and glycogen phosphorylase enzymes. The most potent non toxic compound 40 exhibited about 58% ex vivo activity at MIC of 3.12 μg/mL. The present study opens a new gate to synthesize antitubercular agents for diabetic TB patients. In silico docking studies indicate that mycobacterial dihydrofolate reductase is the possible target of these compounds.

• Hydroxamates can distinguish between NAD+ and ATP -dependent DNA ligases

  Authors: Vandna Kukshal, Mridul Mishra, Taran Khanam, Divya Dube, Deepti Chopra, Arya Ajay, Rahul Sharma, Rama Pati Tripathi, Ravishankar Ramachandran

  medicinal chemistry communication. 01/2011;

• Towards novel antifilarial drugs: challenges and recent developments.

  Authors: Prashant Kumar Singh, Arya Ajay, Susheela Kushwaha, Rama Pati Tripathi, Shailja Misra-Bhattacharya

  Future medicinal chemistry. 02/2010; 2(2):251-83.

  Filariasis is caused by thread-like nematode worms, classified according to their presence in the vertebrate host. The cutaneous group includes Onchocerca volvulus, Loa loa and MansonellaFilariasis is caused by thread-like nematode worms, classified according to their presence in the vertebrate host. The cutaneous group includes Onchocerca volvulus, Loa loa and Mansonella streptocerca; the lymphatic group includes Wuchereria bancrofti, Brugia malayi and Brugia timori and the body cavity group includes Mansonella perstans and Mansonella ozzardi. Lymphatic filariasis, a mosquito-borne disease, is one of the most prevalent diseases in tropical and subtropical countries and is accompanied by a number of pathological conditions. In recent years, there has been rapid progress in filariasis research, which has provided new insights into the pathogenesis of filarial disease, diagnosis, chemotherapy, the host-parasite relationship and the genomics of the parasite. Together, these insights are assisting the identification of novel drug targets and the discovery of antifilarial agents and candidate vaccine molecules. This review discusses the antifilarial activity of various chemical entities, the merits and demerits of antifilarial drugs currently in use, their mechanisms of action, in addition to antifilarial drug targets and their validation.

• Leishmania donovani: oral therapy with glycosyl 1,4-dihydropyridine analogue showing apoptosis like phenotypes targeting pteridine reductase 1 in intracellular amastigotes.

  Authors: Jaspreet Kaur, Nasib Singh, Biswajit Kumar Singh, Anuradha Dube, Rama Pati Tripathi, Prashant Singh, Neeloo Singh

  Experimental parasitology. 02/2010; 125(3):310-4.

  Glycosyl 1,4-dihydropyridine analogue (2,6-dimethyl-4-(3-O-benzyl-1,2-O-isopropylidene-beta-l-threo pentofuranos-4-yl)-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester) synthesizedGlycosyl 1,4-dihydropyridine analogue (2,6-dimethyl-4-(3-O-benzyl-1,2-O-isopropylidene-beta-l-threo pentofuranos-4-yl)-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester) synthesized in our laboratory, inhibited Leishmania donovani infection in vitro and in hamsters (Mesocricetus auratus) when administered orally. This analogue is nontoxic, cell-permeable and orally effective. This glycosyl dihydropyridine analogue functioned through arrest of cells in sub-G0/G1-phase, triggering mitochondrial membrane depolarization-mediated programmed cell death of the intracellular amastigotes.

• Leishmania donovani: A glycosyl dihydropyridine analogue induces apoptosis like cell death via targeting pteridine reductase 1 in promastigotes.

  Authors: Jaspreet Kaur, Biswajit Kumar Singh, Rama Pati Tripathi, Prashant Singh, Neeloo Singh

  Experimental parasitology. 08/2009;

  Targeting of pteridine reductase1 (PTR1) in Leishmania is essential for development of successful antifolate chemotherapy. In search for specific inhibitors of PTR1 we have previously reported phenylTargeting of pteridine reductase1 (PTR1) in Leishmania is essential for development of successful antifolate chemotherapy. In search for specific inhibitors of PTR1 we have previously reported phenyl 1, 4-dihydropyridine ring as the lead structure showing antileishmanial efficacy in vitro and by the oral route in vivo. In this study we present programmed cell death inducing potential of this glycosyl dihydropyridine analogue (2, 6-dimethyl-4-(3-O-benzyl-1, 2-O-isopropylidene-beta-L-threo-pentofuranos-4-yl)-1-phenyl-1, 4-dihydro-pyridine-3, 5-dicarboxylic acid diethyl ester). Flow cytometric analysis revealed that this analogue induces cell cycle arrest at G2/M phase with subsequent increase in sub-G1 peak. Incubation of Leishmania promastigotes with this analogue causes exposure of phosphatidylserine to the outer leaflet of plasma membrane, formation of reactive oxygen species, depolarization of mitochondrial membrane potential and concomitant nuclear alterations that included DNA fragmentation. The results from this study on promastigotes give important lead to investigate further in intracellular amastigotes, the biologically relevant parasite stage in host macrophages.

• Organocatalyzed highly atom economic one pot synthesis of tetrahydropyridines as antimalarials.

  Authors: Mridul Misra, Swaroop Kumar Pandey, Vivek Parashar Pandey, Jyoti Pandey, Renu Tripathi, Rama Pati Tripathi

  Bioorganic & medicinal chemistry. 01/2009;

  A highly atom economic one pot synthesis of tetrahydropyridines was achieved by l-proline/TFA catalysed multicomponent reaction of beta-keto-esters, aromatic aldehydes and anilines. The synthesizedA highly atom economic one pot synthesis of tetrahydropyridines was achieved by l-proline/TFA catalysed multicomponent reaction of beta-keto-esters, aromatic aldehydes and anilines. The synthesized compounds were screened against Plasmodiumfalciparum in vitro and one of them showed antimalarial activity with MIC as low as 0.09mug/mL.

• Aldol reaction of beta-C-glycosylic ketones: synthesis of C-(E)-cinnamoyl glycosylic compounds as precursors for new biologically active C-glycosides.

  Authors: Surendra Singh Bisht, Jyoti Pandey, Anindra Sharma, Rama Pati Tripathi

  Carbohydrate research. 08/2008; 343(9):1399-406.

  A series of beta-C-glycosylic ketones were prepared starting from d-glucose, d-xylose, d-mannose, and cellobiose. The beta-C-glycosylic ketones on aldol condensation with different aromatic aldehydesA series of beta-C-glycosylic ketones were prepared starting from d-glucose, d-xylose, d-mannose, and cellobiose. The beta-C-glycosylic ketones on aldol condensation with different aromatic aldehydes in the presence of a suitable organocatalyst led to the formation of respective C-(E)-cinnamoyl glycosides stereoselectively in good yields as precursors for the synthesis of biologically active compounds.

• NAD(+)-dependent DNA ligase: a novel target waiting for the right inhibitor.

  Authors: Namrata Dwivedi, Divya Dube, Jyoti Pandey, Biswajit Singh, Vandna Kukshal, Ravishankar Ramachandran, Rama Pati Tripathi

  Medicinal research reviews. 08/2008; 28(4):545-68.

  DNA ligases (EC.6.5.1.1) are key enzymes that catalyze the formation of phosphodiester bonds at single stranded or double stranded breaks between adjacent 5' phosphoryl and 3' hydroxyl groups of DNA.DNA ligases (EC.6.5.1.1) are key enzymes that catalyze the formation of phosphodiester bonds at single stranded or double stranded breaks between adjacent 5' phosphoryl and 3' hydroxyl groups of DNA. These enzymes are important for survival because they are involved in major cellular processes like DNA replication/repair and recombination. DNA ligases can be classified into two groups on the basis of their cofactor specificities. NAD(+)-dependent DNA ligases are present in bacteria, some entomopox viruses and mimi virus while ATP-dependent DNA ligases are ubiquitous. The former have recently been drawing a lot of attention as novel targets for antibiotics to overcome current drug resistance issues. Currently a diverse range of inhibitors have been identified. There are several issues to be addressed in the quest for optimized inhibitors of the enzyme. In the first part of the review we summarize current structural work on these enzymes. Subsequently we describe the currently available classes of inhibitors. We also address modalities to improve the specificity and potencies of new inhibitors identified using protein structure based rational approaches. In conclusion, NAD(+)-dependent ligases show great promise and represent a novel drug target whose time has come.

• Leishmania donovani pteridine reductase 1: Biochemical properties and structure-modeling studies.

  Authors: Pranav Kumar, Ashutosh Kumar, Shyam Sundar Verma, Namrata Dwivedi, Nasib Singh, Mohammad Imran Siddiqi, Rama Pati Tripathi, Anuradha Dube, Neeloo Singh

  Experimental parasitology. 07/2008;

  Pteridine reductase 1 (PTR1, EC 1.5.1.33) is a NADPH dependent short-chain reductase (SDR) responsible for the salvage of pterins in the protozoan parasite Leishmania. This enzyme acts as a metabolicPteridine reductase 1 (PTR1, EC 1.5.1.33) is a NADPH dependent short-chain reductase (SDR) responsible for the salvage of pterins in the protozoan parasite Leishmania. This enzyme acts as a metabolic bypass for drugs targeting dihydrofolate reductase, therefore, for successful antifolate chemotherapy to be developed against Leishmania, it must target both enzyme activities. Based on homology model drawn on recombinant pteridine reductase isolated from a clinical isolate of L. donovani, we carried out molecular modeling and docking studies with two compounds of dihydrofolate reductase specificity showing promising antileishmanial activity in vitro. Both the inhibitors appeared to fit well in the active pocket revealing the tight binding of the carboxylic acid ethyl ester group of pyridine moiety to pteridine reductase and identify the important interactions necessary to assist the structure based development of novel pteridine reductase inhibitors.

• Preparation and reactions of sugar azides with alkynes: synthesis of sugar triazoles as antitubercular agents.

  Authors: Biswajit Kumar Singh, Amit Kumar Yadav, Brijesh Kumar, A Gaikwad, Sudhir Kumar Sinha, Vinita Chaturvedi, Rama Pati Tripathi

  Carbohydrate research. 06/2008; 343(7):1153-62.

  5-azido-5-deoxy-xylo-, ribo-, and arabinofuranoses were prepared by the reaction of the respective 5-O-(methanesulfonyl) or p-toluenesulfonyl derivatives with NaN3 in DMF. The intermediate5-azido-5-deoxy-xylo-, ribo-, and arabinofuranoses were prepared by the reaction of the respective 5-O-(methanesulfonyl) or p-toluenesulfonyl derivatives with NaN3 in DMF. The intermediate 5-azido-5-deoxy glycofuranoses on 1,3-cycloaddition with different alkynes in the presence of CuSO4 and sodium ascorbate gave the corresponding sugar triazoles in very good yields. The synthesized sugar triazoles were evaluated for their antitubercular activity against Mycobacterium tuberculosis H37Rv, where one of the compounds displayed mild antitubercular activity in vitro with MIC 12.5 microg/mL.

• Synthesis of azatricyclodiones & octahydro-benzo[f]isoindoles and their antimicrobial evaluation.

  Authors: Nisha Saxena, Nimisha Singh, Mridul Mishra, G B Shiva Keshava, Praveen Kumar Shukla, Rama Pati Tripathi

  Journal of enzyme inhibition and medicinal chemistry. 05/2008;

  A series of azatricyclodiones and octahydro-benzo[f]isoindoles have been synthesized by (4+2) Diels-Alder cycloaddition of maleimides with furfuryl amine. Reaction of azatricyclodiones withA series of azatricyclodiones and octahydro-benzo[f]isoindoles have been synthesized by (4+2) Diels-Alder cycloaddition of maleimides with furfuryl amine. Reaction of azatricyclodiones with isocyanates led to the respective ureides. All of the compounds were screened against a number of bacteria and fungi. One of the compounds (2) displayed moderate antitubercular activity while two compounds (2) and (4) inhibited the fungal growth at 25 mug/mL.

• Pharmacokinetics and excretion of the novel anti-tuberculosis compound 1,2:5,6-di-O-isopropylidene-3-O-(phenyl cyclopropyl methanonyl)-alpha-D-glucofuranose (S-001-14) after oral doses in rats. Development of a sensitive and reproducible high performance liquid chromatography-UV method for the determination of the test compound in rat serum.

  Authors: Jawahar Lal, Rama Pati Tripathi, Ram Chandra Gupta

  Arzneimittel-Forschung. 02/2008; 58(8):410-8.

  A sensitive and reproducible high performance liquid chromatography (HPLC)-UV method for the determination of the novel anti-tuberculosis compound 1,2:5,6-di-O-isopropylidene-3-O-(phenyl cyclopropylA sensitive and reproducible high performance liquid chromatography (HPLC)-UV method for the determination of the novel anti-tuberculosis compound 1,2:5,6-di-O-isopropylidene-3-O-(phenyl cyclopropyl methanonyl)-alpha-D-glucofuranose (S-001-14) has been developed and validated in rat serum, urine and feces. Following extraction with hexane at alkaline pH, samples were separated on a reverse phase C18 column and quantified using UV detection at 267 nm. The mobile phase was 70% acetonitrile in ammonium acetate buffer (10 mmol/L, pH 6.0) with a flow rate of 1.0 ml/min. The method was used to determine the pharmacokinetics and excretion of S-001-14 after oral doses in rats. Linearity was satisfactory over the concentration range of 5-500 ng/ml (r2, > 0.99). Recoveries were > 90% and were consistent throughout the calibration range. The precision and accuracy were acceptable as indicated by relative standard deviation ranging from 2.72 to 9.54%, bias values ranging from 1.62 to 12.05%. Moreover, S-001-14 was stable in rat serum after being subjected to three freeze-thaw cycles and for 30 days on storage at - 60 degrees C. The method was used to determine the serum concentration-time profiles for S-001-14 after oral doses of 4, 100 and 200 mg/kg in rats. A linear pharmacokinetics was found in rats at 100 and 200 mg/kg doses with a long elimination half-life (approximately 24 h), wide distribution and bioavailability of approximately 13%. The excretion study after the 100 mg/kg oral dose revealed that S-001-14 was excreted in urine (0.002 +/- 0.001%) and feces (15.6 +/- 3.5%).

• NAD+-dependent DNA ligase (Rv3014c) from M. tuberculosis: Strategies for inhibitor design

  Authors: Divya Dube, Vandna Kukshal Sandeep Kumar Srivastava, Rama Pati Tripathi, Ravishankar Ramachandran

  MEDICINAL CHEMISTRY RESEARCH. 01/2008;

• Synthesis and biological evaluation of potential modulators of malarial glutathione-S-transferase(s).

  Authors: Rumana Ahmad, Arvind K Srivastava, Rama Pati Tripathi, Sanjay Batra, Rolf D Walter

  Journal of enzyme inhibition and medicinal chemistry. 07/2007; 22(3):327-42.

  Glutathione-S-transferase(s) (E.C.2.5.1.18, GSTs) have been investigated in parasitic protozoans with respect to their biochemistry and they have been identified as potential vaccine candidates inGlutathione-S-transferase(s) (E.C.2.5.1.18, GSTs) have been investigated in parasitic protozoans with respect to their biochemistry and they have been identified as potential vaccine candidates in protozoan parasites and as a target in the synthesis of new antiparasitic agents. In a search towards the identification of novel biochemical targets for antimalarial drug design, the area of Plasmodium glutathione metabolism provides a number of promising chemotherapeutic targets. GST activity was determined in various subcellular fractions of malarial parasites Plasmodium yoelii and was found to be localized mainly in the cytosolic fraction (specific activity, c. 0.058 +/- 0.016 micromol/min/mg protein). Hemin, a known inhibitor of mammalian GST(s), maximally inhibited this enzyme from P. yoelii to nearly 86%. In a search towards synthetic modulators of malarial GST(s), 575 compounds belonging to various chemical classes were screened for their effect on crude GST from P. yoelii and 92 compounds belonging to various chemical classes were studied on recombinant GST from P. falciparum. Among all the compounds screened, 83 compounds inhibited/stimulated the enzyme from P. yoelii/P. falciparum to the extent of 40% or more.

• Recent developments in search of antifilarial agents.

  Authors: Rama Pati Tripathi, Diksha Katiyar, Namrata Dwivedi, Biswajit K Singh, Jyoti Pandey

  Current medicinal chemistry. 02/2006; 13(27):3319-34.

  Filariasis, caused by spirunid nematodes, is one of the most prevalent diseases of tropical and subtropical countries and encompasses a number of different pathological conditions. It has greatFilariasis, caused by spirunid nematodes, is one of the most prevalent diseases of tropical and subtropical countries and encompasses a number of different pathological conditions. It has great impact on the socioeconomic conditions of the people affected with this disease. The most common type of filariasis is a lymphatic filariasis caused by a parasite that lives in human lymph system. Like malaria, it is also caused by mosquito bites. The life cycle of the parasite, pathogenesis and diagnosis of filariasis have been briefly reviewed here in. Different strategies to control this disease have been discussed with major emphasis on the mechanisms, merits and demerits of the existing drugs and the drugs under pipeline. New antifilarial prototypes discovered recently and finally the future perspective to control the disease have also been elucidated.

• NAD+-dependent DNA Ligase (Rv3014c) from Mycobacterium tuberculosis. Crystal structure of the adenylation domain and identification of novel inhibitors.

  Authors: Sandeep Kumar Srivastava, Rama Pati Tripathi, Ravishankar Ramachandran

  The Journal of biological chemistry. 09/2005; 280(34):30273-81.

  DNA ligases utilize either ATP or NAD+ as cofactors to catalyze the formation of phosphodiester bonds in nicked DNA. Those utilizing NAD+ are attractive drug targets because of the unique cofactorDNA ligases utilize either ATP or NAD+ as cofactors to catalyze the formation of phosphodiester bonds in nicked DNA. Those utilizing NAD+ are attractive drug targets because of the unique cofactor requirement for ligase activity. We report here the crystal structure of the adenylation domain of the Mycobacterium tuberculosis NAD+-dependent ligase with bound AMP. The adenosine nucleoside moiety of AMP adopts a syn-conformation. The structure also captures a new spatial disposition between the two subdomains of the adenylation domain. Based on the crystal structure and an in-house compound library, we have identified a novel class of inhibitors for the enzyme using in silico docking calculations. The glycosyl ureide-based inhibitors were able to distinguish between NAD+- and ATP-dependent ligases as evidenced by in vitro assays using T4 ligase and human DNA ligase I. Moreover, assays involving an Escherichia coli strain harboring a temperature-sensitive ligase mutant and a ligase-deficient Salmonella typhimurium strain suggested that the bactericidal activity of the inhibitors is due to inhibition of the essential ligase enzyme. The results can be used as the basis for rational design of novel antibacterial agents.

• Mycobacterium tuberculosis NAD+-dependent DNA ligase is selectively inhibited by glycosylamines compared with human DNA ligase I.

  Authors: Sandeep Kumar Srivastava, Divya Dube, Neetu Tewari, Namrata Dwivedi, Rama Pati Tripathi, Ravishankar Ramachandran

  Nucleic acids research. 02/2005; 33(22):7090-101.

  DNA ligases are important enzymes which catalyze the joining of nicks between adjacent bases of double-stranded DNA. NAD+-dependent DNA ligases (LigA) are essential in bacteria and are absent inDNA ligases are important enzymes which catalyze the joining of nicks between adjacent bases of double-stranded DNA. NAD+-dependent DNA ligases (LigA) are essential in bacteria and are absent in humans. They have therefore been identified as novel, validated and attractive drug targets. Using virtual screening against an in-house database of compounds and our recently determined crystal structure of the NAD+ binding domain of the Mycobacterium tuberculosis LigA, we have identified N1, N(n)-bis-(5-deoxy-alpha-D-xylofuranosylated) diamines as a novel class of inhibitors for this enzyme. Assays involving M.tuberculosis LigA, T4 ligase and human DNA ligase I show that these compounds specifically inhibit LigA from M.tuberculosis. In vitro kinetic and inhibition assays demonstrate that the compounds compete with NAD+ for binding and inhibit enzyme activity with IC50 values in the microM range. Docking studies rationalize the observed specificities and show that among several glycofuranosylated diamines, bis xylofuranosylated diamines with aminoalkyl and 1, 3-phenylene carbamoyl spacers mimic the binding modes of NAD+ with the enzyme. Assays involving LigA-deficient bacterial strains show that in vivo inhibition of ligase by the compounds causes the observed antibacterial activities. They also demonstrate that the compounds exhibit in vivo specificity for LigA over ATP-dependent ligase. This class of inhibitors holds out the promise of rational development of new anti-tubercular agents.

• A versatile synthesis of dihydropyrimidinone C-nucleosides.

  Authors: Ram Chandra Mishra, Diksha Katiyar, Neetu Tewari, Rama Pati Tripathi

  Nucleosides, nucleotides & nucleic acids. 02/2004; 23(3):531-44.

  A versatile synthesis of N-substituted dihydropyrimidinone C-nucleosides (20-29) is described. Glycosyl amino esters (3-9), obtained by reductive alkylation of glycosyl amino esters 1 and 2, onA versatile synthesis of N-substituted dihydropyrimidinone C-nucleosides (20-29) is described. Glycosyl amino esters (3-9), obtained by reductive alkylation of glycosyl amino esters 1 and 2, on condensation with different isocyanates afforded respective ureido derivatives (10-19) in good to quantitative yields. The latter on cyclative amidation with a combination of DBU/TBAB (tetrabutylammonium bromide)/4A molecular sieve gave the corresponding nucleosides (20-29) in good yields.

• Synthesis and antifilarial evaluation of 7-O-acetamidyl-4-alkyl-2H-1-benzopyran-2-ones.

  Authors: Diksha Katiyar, Vinod Kumar Tiwari, Rama Pati Tripathi, Velurijagan Mohan Reddy, Shailza Mishra Bhattacharya, Jitendra Kumar Saxena

  Arzneimittel-Forschung. 02/2003; 53(12):857-63.

  A series of 7-O-acetamidyl-4-alkyl-2H-1-benzopyran-2-ones (5-23) has been synthesized by amidation of 7-O-(carbethoxymethyl)-4-alkyl-2H-1-benzopyran-2-ones (2a, 2b) with different primary andA series of 7-O-acetamidyl-4-alkyl-2H-1-benzopyran-2-ones (5-23) has been synthesized by amidation of 7-O-(carbethoxymethyl)-4-alkyl-2H-1-benzopyran-2-ones (2a, 2b) with different primary and secondary amines in fair to good yield. The resulting compounds were screened for their filarial DNA topoisomerase inhibitory activity under in vivo condition in Setaria cervi. The compounds were tested in vitro against Brugia malayi. A few of the compounds possess promising antifilarial activity.

• Leishmania donovani: A glycosyl dihydropyridine analogue induces apoptosis like cell death via targeting pteridine reductase 1 in promastigotes

  Authors: Jaspreet Kaur, Biswajit Kumar Singh, Rama Pati Tripathi, Prashant Singh, Neeloo Singh

  Experimental Parasitology.

  Targeting of pteridine reductase 1 (PTR1) in Leishmania is essential for development of successful antifolate chemotherapy. In search for specific inhibitors of PTR1 we have previously reportedTargeting of pteridine reductase 1 (PTR1) in Leishmania is essential for development of successful antifolate chemotherapy. In search for specific inhibitors of PTR1 we have previously reported phenyl 1,4-dihydropyridine ring as the lead structure showing antileishmanial efficacy in vitro and by the oral route in vivo. In this study, we present programmed cell death inducing potential of this glycosyl dihydropyridine analogue (2,6-dimethyl-4-(3-O-benzyl-1,2-O-isopropylidene-β-l-threo-pentofuranos-4-yl)-1-phenyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid diethyl ester). Flow cytometric analysis revealed that this analogue induces cell cycle arrest at G2/M phase with subsequent increase in sub-G1 peak. Incubation of Leishmania promastigotes with this analogue causes exposure of phosphatidylserine to the outer leaflet of plasma membrane, formation of reactive oxygen species, depolarization of mitochondrial membrane potential and concomitant nuclear alterations that included DNA fragmentation. The results from this study on promastigotes give important lead to investigate further in intracellular amastigotes, the biologically relevant parasite stage in host macrophages.