Seminar: Organic chemistry, Medicinal chemistry | May 23 | 3 p.m.-4 p.m. | Room 3.2.16 (FCUL C3)
Virinder S. Parmar, Nanoscience Program, CUNY-Graduate Center and Departments of Chemistry, City College & Medgar Evers College, The City University of New York, United States
Natural Products-Inspired Discovery and Development of Novel Antimicrobials, Anti-inflammatory and Antiplatelet Agents
Host: Amélia Rauter
We have extensively worked on several medicinally important plants used in the traditional Indian and Chinese systems of medicine and isolated a large number of novel compounds belonging to different classes (alkaloids, polyphenols, steroids, amides, terpenoids, etc.). Several of these compounds have shown interesting biological activities, remarkable of them has been our extensive work on polyphenol acetates leading to the discovery of a fundamental biochemical pathway involving acetyl CoA-independent enzymatic protein acetylation. Our seminal investigations have highlighted the unique biochemical and pharmacological action of polyphenol acetates. These act as the substrates for the well-known protein calreticulin and transfer acetyl groups to certain receptor enzymes, such as cytochrome P-450 linked mixed function oxidases (MFO), NADPH cytochrome c reductase, Nitric Oxide Synthase (NOS), protein kinase c (PKC) and glutathione S-transferase (GST) resulting in modulation of their catalytic activities. The purified enzyme from buffalo liver in the presence of 7,8-diacetoxy-4 methylcoumarin (DAMC) and several other polyphenol acetates was found to significantly enhance the NOS activity in human platelets and caused significant vasorelaxation. These polyphenol acetates and several natural products were also found to lower PKC levels and suppress the ICAM-1 and VCAM-1 expression and were found to be good anti-inflammatory & anti-asthmatic agents. Further, acetyl polyphenols and several other classes of natural products were also found to be excellent inhibitors of chemical and radiation induced clastogenicity, and antimicrobial agents against various deadly fungal & bacterial infections viz. botulism and aspergillosis.
Details of these studies will be presented at the Symposia.
Key References:
E Kohli, M Gaspari, HG Raj, VS Parmar, SK Sharma, J van der Greef, R Kumari, G Gupta, Seema, P Khurana, YK Tyagi, AC Watterson and CE Olsen. Acetoxy drug: protein transacetylase of buffalo liver — characterization and mass spectrometry of the acetylated protein product. Biochimica et Biophysica Acta 1698, 2004, 55– 66.
S Kumar, P Arya, C Mukherjee, BK Singh, N Singh, VS Parmar, AK Prasad and B Ghosh. Novel aromatic ester from Piper longum and its analogues inhibit expression of cell adhesion molecules on endothelial cells. Biochemistry 44, 2005, 15944-15952.
ME Bracke, BWA Vanhoecke, L Derycke, S Bolca, S Possemiers, A Heyerick, CV Stevens, DD Keukeleriem, HT Depypere, W Verstraete, CA Williams, ST McKenna, S Tomar, D Sharma, AK Prasad, AL DePass and VS Parmar. Plant polyphenolics as anti-invasive cancer Agents. Anticancer Agents in Medicinal Chemistry 8, 2008, 171-185.
A Goel, AK Prasad, VS Parmar, B Ghosh and N Saini. Apotogenic effect of 7,8-diacetoxy-4-methylcoumarin and 7,8-diacetoxy-4-methylthiocoumarin in human lung adenocarcinoma cell line: Role of NF-kB, AkT, ROS and MAP kinase pathway. Chemico-Biological Interactions 179, 2009, 363-374.
AK Chillar, V Yadav, A Kumar, M Kumar, VS Parmar, AK Prasad and GL Sharma. Differential expression of Aspergillus fumigatus protein in response to treatment with a novel antifungal compound, diethyl 4-(4-methoxyphenyl-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarboxylate. Mycoses 52, 2009, 223-227.
V Kumar, S Kumar, M Hassan, H Wu, RK Thimmulappa, A Kumar, SK Sharma, VS Parmar, S Biswal and SV Malhotra. Novel chalcone derivatives as potent Nf2 activators on mice and human lung epithelial cells. Journal of Medicinal Chemistry 54, 2011, 4147-4159.
K Macáková, Z Reháková, P Mladenka, J Karlícková, T Filipský, M Ríha, AK Prasad, VS Parmar, L ek Jahodár, P Pávek, R Hrdina and L Saso. In vitro platelet antiaggregatory properties of 4-methylcoumarins. Biochimie 2012, 94, 2681-2686.
A Kumar, S Sushama, S Manral, S Sinha, R Joshi, U Singh, V Rohil, AK Prasad, VS Parmar and HG Raj. Calreticulin transacetylase mediated activators of human platelet nitric oxide synthase by acetyl group donor compounds. Nitric Oxide: Biology and Chemistry 26, 2012, 9-19.
S Kumar, BK Singh, AK Prasad, VS Parmar, S Biswal and B Ghosh. Ethyl 3′,4′,5′-trimethoxythionocinnamate modulates NF-κB and Nrf2 transcription factors. European Journal of Pharmacology 700, 2013, 32–41.
S Kumar, S Malhotra, AK Prasad, EV Van der Eycken, ME Bracke, WG Stetler-Stevenson, VS Parmar and B Ghosh. Anti-inflammatory and antioxidant properties of Piper species: A perspective from screening to molecular mechanisms. Current Topics in Medicinal Chemistry 15, 2015, 886-893.
K Venkateswaran, A Shrivastava, PK Agrawala, AK Prasad, N Kalra, PR Pandey, K Manda, HG Raj, VS Parmar and BS Dwarakanath. Mitigation of radiation-induced hematopoietic injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice. Nature Scientific Reports 6:37305, 2016, DOI: 10.1038/srep37305 (pp. 1-20).
M Balhara, R Chaudhary, S Ruhil, B Singh, N Dahiya, VS Parmar, PK Jaiwal and AK Chhillar. Siderophores; iron scavengers: The novel and promising targets for pathogen specific antifungal therapy. Expert Opinion on Therapeutic Targets 20, 2016, 1477-1489.
S Malhotra, S Singh, N Rana, S Tomar, P Bhatnagar, M Gupta, SK Singh, BK Singh, AK Chhillar, AK Prasad, C Len, P Kumar, KC Gupta, AJ Varma, RC Kuhad, GL Sharma, VS Parmar and NGJ Richards. Chemoenzymatic synthesis, nanotization and anti-Aspergillus activity of optically enriched fluconazole analogues. Antimicrobial Agents and Chemotherapy 61, 2017, e00273-17, doi:10.1128/AAC.00273-17.
VD Kancheva, AK Slavova-Kazakova, SE Angelova, SK Singh, S Malhotra, BK Singh, L Saso, AK Prasad and VS Parmar. Protective effects of 4-methylcoumarins and related compounds as radical scavengers and chain-breaking antioxidants. Biochimie 140, 2017, 133-145.
HK Tiwari, P Kumar, N Jatana, K Kumar, S Garg, L Narayanan, PS Sijwali, KC Pandey, N Yu Gorobets, BN Dunn, VS Parmar and BK Singh. In vitro antimalarial evaluation of piperazine- and piperazine-based chalcones: Inhibition of falcipain-2 and plasmepsin II hemoglobinases activities from Plasmodium falciparum. Chemistry Select 2(25), 2017, 7684-7690.
K Venkateswaran, A Verma, AN Bhatt, A Shrivastava, K Manda, HG Raj, AK Prasad, C Len, VS Parmar and BS Dwarakanath. Emerging roles of calreticulin in cancer: Implications for therapy. Current Protein & Peptide Science 19, 2018, 344-357.
VD Kancheva, AK Slavova-Kazakova, SE Angelova, P Kumar, S Malhotra, BK Singh, L Saso, AK Prasad and VS Parmar. Protective effects of new antioxidant compositions of 4-methylcoumarins and related compounds with DL-α-tocopherol and L-ascorbic acid. Journal of the Science of Food and Agriculture 98, 2018, 3784-3794.
E Profumo, B Buttari, L Tinaburri, D. D’Arcangelo, M Sorice, A Capozzi, T Garofalo, A Facchiano, R Businaro, P Kumar, BK Singh, VS Parmar, L Saso and R Rigano. Oxidative stress induces HSP90 up-regulation on the surface of primary human endothelial cells: Role of the antioxidant 7,8-dihydroxy-4-methylcoumarin to prevent HSP90 exposure to the immune system. Oxidative Stress and Cellular Longevity 2018, 2018, Article ID 2373167, 9 pages, doi: 10.1155/2018/2373167.
KB Patel, S Cai, M Adler, BK Singh, VS Parmar and BR Singh. Natural compounds and their analogues as potent antidotes against the most poisonous bacterial toxin. Applied and Environmental Microbiology 84, 2018, DOI:10.1128/AEM.01280-18.
K Venkateswaran, A Shrivastva, PK Agrawala, AK Prasad, SC Devi, K Manda, VS Parmar and BS Dwarakanath. Mitigation of radiation-induced gastro-intestinal injury by the polyphenolic acetate 7, 8-diacetoxy-4-methylthiocoumarin in mice. Nature Scientific Reports 9:14134, 2019, https://doi.org/10.1038/s41598-019-50785-x (pp. 1-17).
S Dahiya, AK Chhillar, N Sharma, P Choudhary, A Punia, M Balhara, K Kaushik and VS Parmar. Candida auris and nosocomial infection. Current Drug Targets 21, 2020, 365-373.
K Venkateswaran, A Shrivastava, AK Prasad, VS Parmar and BS Dwarakanath. Developing polyphenolic acetates as radiation countermeasure agents: Current status and future perspectives. Drug Discovery Today 25, 2020, 781-786.
KB Patel, O Kononova, S Cai, V Barsegov, VS Parmar, R Kumar and BR Singh. Botulinum neurotoxin inhibitor binding dynamics and kinetics relevant for drug design. Biochimica et Biophysica Acta (BBA) – General Subjects, 2021, https://doi.org/10.1016/j.bbagen.2021.129933.
A Kumar, P Kaushik, S Incerpi, JZ Pedersen, S Goel, AK Prasad, V Rohil, VS Parmar, L Saso and C Len. Evaluation of the free radical scavenging activities of ellagic acid and ellagic acid peracetate by EPR spectrometry. Molecules 26, 2021, 4800. https://doi.org/10.3390/molecules26164800.
S Dahiya, N Sharma, A Punia, P Choudhary, P Gulia, VS Parmar and AK Chhillar. Antimycotic drugs and their mechanisms of resistance to Candida species. Current Drug Targets 23, 2022, 116-125.
K Venkateswaran, A Shrivastava, PK Agrawala, AK Prasad, K Manda, VS Parmar and BS Dwarakanath. Immune-modulation by 7, 8-diacetoxy-4-methylthiocoumarin in total body-irradiated mice: Implications for the mitigation of radiation-induced hematopoietic injury. Life Sciences 311, 2022, https://doi.org/10.1016/j.lfs.2022.121140.
A Behl, S Solanki, SK Paswan, TK Datta, AK Saini, RV Saini, VS Parmar, VK Thakur, S Malhotra and AK Chhillar. Biodegradable PEG-PCL nanoparticles for co-delivery of MUC1 inhibitor and doxorubicin for the confinement of triple-negative breast cancer. Journal of Polymers and the Environment 31, 2023, 999–1018.
A Behl, ZA Wani, NN Das, VS Parmar, C Len, S Malhotra and AK Chhillar. Monoclonal antibodies in breast cancer: A critical appraisal. Critical Reviews in Oncology/Hematology 183, 2023, 103915.
HK Sharma, P Gupta, D Nagpal, M Mukherjee, VS Parmar and V Lather. Natural compounds as the prospective inhibitors of antibacterial drug resistance targets in Staphylococcus aureus. Fitotrepia 170, 2023.