Natural Products Chemistry (Plants) Division

Indian Institute of Integrative Medicine has a state art of facility in the area of natural product chemistry with expertise in all the relevant fields needed for drug development especially drugs based on traditional systems of healthcare and validated as per modern systems. Prospecting the Natural Products of the Himalayan region including high altitude as well as other parts of the country is one of the broad objectives of the group. The division is actively engaged in exploration of natural products from both plants as well as microbial sources. Different research activities carried out at NPC division is summarized in figure 1 as a flow chart.

Figure 1: Different research activities pursued at Natural Product Chemistry division

Some of the representative examples of plant and microbes based secondary metabolites isolated at CSIR-IIIM Jammu are shown in Figure 2.

fig 1

fig 2

Figure 2. Representative secondary metabolites isolated from plants & microbes

Secondary metabolites isolated from plant and microbes were used as starting materials to produce other novel compounds (semisynthesis) with distinct chemical and medicinal properties. Further, Diversity Oriented Synthesis (DOS) of natural products were being carried out for the discovery of novel, biologically interesting small molecules. Some representative examples are shown in Figure 3.

fig 3

  • To become a Centre of Excellence in the Natural Product Chemistry
  • In accordance with the missions and goals of the Institute, the group strives to contribute towards its development and recognition as one of the premier national institutes in the area of natural products chemistry by Phytopharmaceutical and herbal drug development.
  • Collection of samples from varied ecological niches and other sources.
  • Development of SOPs and isolation of new bioactive molecules from different sources from plants, microbial strains and animals.
  • Diversifying microbial Natural Product strains and extract libraries, characterization of molecules from microbes and evaluation of their biological potency.
  • Isolation and structure elucidation of bioactive natural compounds from plants, marine sponges and microbes.  These studies have outcome both in the realm of botanical and phytopharmaceutical drugs and modern drug discovery.
  • Fine tuning of bioactivity of the molecules with better activity and less toxicity
  • Natural Products Division at CSIR-IIIM is mainly engaged in the discovery and development of botanicals and phytopharmaceuticals for the treatment of disease based on secondary metabolites from nature. The Division is engaged to find for Natural Product lead compounds for drug development, and to understand their mechanism of action with available modern and cutting-edge technology to realize our goal, and have unique expertise in the structure elucidation of complex natural products.
  • Development of Ayurveda based botanical drugs for the prophylaxis and management of the New Corona Virus Disease (COVID-19).
  • In collaboration with ICGEB and Sun Pharmaceuticals, a Cocculus hirsutus based phytopharmaceutical is being developed by CSIR-IIIM. Drug has shown anti-SARS-CoV-2 effects in-vitro studies conducted in collaboration with ICGEB and Sun Pharmaceuticals. Phase-II Clinical trials on AQCH extract is in progress.
  • The IND application of IIIM-160 (phytopharmaceutical lead) has been filed to DCGI to seek permission for conducting phase I clinical trial in rheumatoid arthritis patients.
  • Purified fraction of different medicinal plant (Cannabis, Epimedium, Piper beetle, Dysoxylum binectariferum, Crocus sativus) devloped for different therapeutic purposes for epilepsy, aphrodisiac, sickle cell anemia, rheumatoid arthritis and Alzheimer’s disease respectively (Phytopharmaceuticals Mission).
  • Development of Clinical therapeutics under Ayush mode.
  • The Division exercises multiple research projects that require identifying new lead molecules.
  • Collection of samples from diverse ecological niches with proper selection
  • Manipulating microbial physiology to activate microbial natural product machinery.
  • Genetically modifying strains for desired microbial Natural Products.
  • Monitoring diversity while reducing redundancy of microbial extracts.
  • Characterization of new molecules from microbes and evaluation of their biological potency.
  • Over the years of research and development, the Division explored huge culturable microbes and isolated many compounds, and found to be novel chemical entities. In addition to this, the Division is engaged in several Drug Discovery projects for CNS, Diabetes and viral infections, and the general idea for all of these is the use of natural substances to discover secondary metabolites that affect biological systems and can be utilized for new treatment.

Following are the instruments which are being used for various kind of analysis:

Dr. Debaraj Mukherjee
Principal Scientist

 

Dr. Payare Lal Sangwan
Principal Scientist

Dr. Prasoon Kumar Gupta
Principal Scientist

 

Dr Bhahwal A. Shah
Senior Scientist

Dr. Mahendra Kumar Verma
Technical Officer

  • Dengue Herbal Project (Advanced Phase, Sun Pharma Limited)
  • Novel Strategy to Generate Drug Like Marine Natural Product Library to Discover Bioactive Compounds (SERB)
  • Fermentation Based Process Development for Production of Tacrolimus Drug (ICMR)
  • Effect of Epigenetic Modifiers on Secondary Metabolite Production in Drug Producing Fungi (SERB)
  • CSIR-Phytopharmaceutical Mission (CSIR)
  • CSIR-Sickle Cell Anaemia Mission (CSIR)
  • CSIR-Aroma Mission (CSIR)
  • Phytopharmaceutical Development of Ficus semicordata -Ham. Ex Sm. as per regulatory guidelines of DCGI (under the phytopharmaceutical   Mission for North East Region (GAP 2180)
  • Discovery of target based novel bioactive natural products from high altitude plants Hippophae rhamnoids (Sebuckthorn) and Grewia asiatica (phalsa) for achieving the pharmacological and cosmetic effects against ultraviolet radiation induced skin damage (photo ageing/ carcinogenesis) (GAP-2167)
  • Development of Phytopharmaceutical product for bovine mastitis (GAP-2141)
  • Creation of national repository of pure natural products (MLP-4013)
  • Natural Product Chemistry and Pharmacology of Medicinal Plants (MLP-4012)

Representative Publications for NPC-Plants

Authors Title Journal
S.K. Rath, S. Singh, S. Kumar, N.A. Wani, R. Rai, I.A. Khan, S. Koul, and P.L. Sangwan. Synthesis of (E)-3-(1-chloro-3,4-dihydronaphthalen-2-yl) acrylic acid substituted amino acid ester derivatives as inhibitors of Staphylococcus aureus NorA efflux pump to combat antimicrobial resistance. Bioorg. Med. Chem. 2020, 27(2). 343-353
P.K. Chinthakindi, S.K. Rath, J. Singh, S. Singh, S. Koul, and P.L. Sangwan. Isolation of isoxanthanol and synthesis of novel derivatives as potential cytotoxic agents. Med. Chem. Res. 2017, 26(10), 2499-2513.
N.A. Dangroo, J. Singh, S.K. Rath, N. Gupta, A. Qayum, S. Singh, and P.L. Sangwan. A convergent synthesis of novel alkyne–azide cycloaddition congeners of betulinic acid as potent cytotoxic agent. Steroids, 2017, 123, 1-12.
N. Gupta, S.K. Rath, A. Qayum, J. Singh, S. Singh, and P.L. Sangwan Synthesis of novel benzylidene analogues of betulinic acid as potent cytotoxic agents. Eur. J. Med. Chem. 2017, 135, 517-530.
N.A. Dangroo, J. Singh, N. Gupta, S.K. Singh, A. Koul, M.A. Khuroo, and P.L. Sangwan. T- and B-cell immunosuppressive activity of novel α-santonin analogs with humoral and cellular immune response in mice. Med. Chem. Comm. 2017, 8, 211-219.
A.A. Dar, N.A. Dangroo, A. Raina, A. Qayum, S.K. Singh, A. Kumar, and P.L. Sangwan. Biologically active xanthones from Codonopsis ovata. Phytochem. 2016, 132, 102-108.
N. Gupta, S. Sharma, A. Raina, N.A. Dangroo, S. Bhushan, and P.L. Sangwan. Synthesis and anti-proliferative evaluation of novel 3,4-dihydro-2H-1,3-oxazine derivatives of bakuchiol. RSC Adv. 2016, 6(108) 106150-106159
A.A. Dar, P.L. Sangwan, I. Khan, N. Gupta, A. Qaudri, S.A. Tasduq, S. Kitchlu, A.K. Sharma, and S. Koul. Simultaneous quantification of eight bioactive secondary metabolites from Codonopsis ovata by validated high performance thin layer chromatography and their antioxidant profile. J. Pharma. Biomed. Anal. 2014, 100: 300-8.
Faheem Rassol, Debashis, Anindya Goswami and Debaraj Mukherjee Regiospecific Synthesis of Ring A Fused Withaferin A Isoxazoline Analogues: Induction of Premature Senescence by W-2b in Proliferating Cancer Cells.

 

Nature Scientific Reports, 2017, 7, 13749.
Khan, I. A.; Singh, A.; Mindala, D. P.; Meena. S.; Gupta Prasoon Preclinical development of gastroprotective botanical candidate from Woodfordia fruticosa (Linn.) Kurz: Chemical standardization, efficacy, pharmacokinetics and safety pharmacology. Journal of Ethanopharmacology 2019, 241, 112023-112056

 

 

Representative Publications for NPC-Microbes

Authors Title Journal
Sharma, V.; Singamaneni, V.; Sharma, N.; Sharma, A.; Arora, D.; Kushwaha, M.; Bhushan, S.; Jaglan, S.; Gupta, Prasoon Valproic acid induces three novel cytotoxic Secondary metabolites in Diaporthe sp., an endophytic fungus from Datura inoxia Mill. Bioorganic and Medicinal Chemistry Letters 2018, 28(12), 2217-2221
Arora, N.; Kumar, S.; Satti, N. K.; Ali, A.; Gupta, Prasoon. Katoch, M. A strain of Streptomyces sp. isolated from rhizospheric soil of Crataegus oxycantha producing nalidixic acid, a synthetic antibiotic. Journal of Applied Microbiology 2018, 124(6), 1393-1400.
Arora, Divya; Chashoo, Gousia; Singamaneni, Venugopal ; Sharma, Nisha; Gupta, Prasoon; Jaglan, Sundeep. Bacillus amyloliquefaciens induces production of a novel blennolide k in co-culture of Setophoma terrestris. Journal of Applied Microbiology 2018, 124 (3), 730-739
Sharma, N.; Kushwaha, M.; Arora, D.; Jain, S.; Singamaneni, V.; Sharma, S.; Shankar, R.; Bhushan, S.; Gupta, Prasoon; ; Jaglan, S. New cytochalasin from Rosellinia sanctae-cruciana, an endophytic fungus of Albizia lebbeck. Journal of Applied Microbilogy 2018, 125(1), 111-120.
Arora, D.; Sharma, N.; Singamaneni, V.; Sharma, V.; Manoj, K.; Abrol, V.; Guru, S.; Sharma, S.; Gupta, A. P.; Bhushan, S.; Jaglan, S.; Gupta, Prasoon. Isolation and characterisation of bioactive metabolites from Xylaria psidii, an endophyte fungus of the medicinal plant Aegle marmelos and their role in mitochondrial dependent apoptosis against pancreatic cancer cells. Phytomedicine 2016, 23, 1312-1320.

 

Deepak K. Sharma, Sundeep Jaglan & Debaraj Mukherjee Isolation and conversion of Penicillic acid to 6- iodo-α -pyran-2,5-dione: A key intermediate for the synthesis of Pectinolide F

 

Synthetic Communications, 2016, 46, 902-908.
Rashmi Sharma, Mallikharjuna Rao Lambu , Urmila,Jamwal ChitraRani, Reena Chib,PriyaWazir, Debaraj Mukherjee, Asha Chaubey, Inshad Ali Khan Escherichia coli N-Acetylglucosamine-1-Phosphate Uridyltransferase /Gluco samine-1- Phosphate-Acetyltransferase (GlmU) Inhibitory Activity of Terreic Acid Isolated from Aspergillus terreus..

 

J Biomol Screen,13,2016.
Debasis Nayak, Archana Katoch, Deepak Sharma, Mir Mohd. Faheem  Souneek Chakraborty,Promod Kumar Sahu,Naveed Anjum Chikan,Hina Amin,  Ajai Prakash Gupta,  Sumit G. Gandhi, Debaraj Mukherjee, Anindya Goswami. Indolylkojyl methane analogue IKM5 potentially inhibits invasion of breast cancer cells via attenuation of GRP78.

 

Breast Cancer Research and Treatment, 2019, DOI.org/10.1007/s10549-019-05301-0
Devari S, Vishwakarma RA, Shah BA et. al. Capsaicin production by Alternaria alternata, an endophytic fungus from Capsicum annum; LC–ESI–MS/MS analysis Phytochemistry, 2014 ,98:183-189.
M Kumar, M Qadri, PR Sharma, A Kumar, SS Andotra, T Kaur, K Kapoor, Shah BA et. al. Tubulin Inhibitors from an Endophytic Fungus Isolated from Cedrus deodara

 

Journal of natural products 76 (2), 194-199

Patents for NPC-Plants

Inventors/ Contributors Title Description Year
A. Kumar, IA Khan, S Koul, PL Sangwan, DM Mondhe, U Nandi, G Singh, MK Tikoo, S Sharma, A Wani, SK Rath, S Singh, MJ Mintoo, RA Vishwakarma. Pharmaceutical composition to enhance the bioavailability/bioefficay of drugs NF0166NF2018 2019
Debaraj Mukherjee & Anindya Goswami Indolylkojyl derivatives as inhibitor of invasion and metastasis in human mammary gland carcinomas. US Patent PCT/IN2018/050060) 2018
S. Bani, A Pandey, I. Khan, S. Koul, P.L. Sangwan, V. Marnickavasagar, M. Rajendran Eurycoma longifolia extract and uses thereof IN 2012DE01039 A 20150731 2015

Patents for NPC-Microbes

Inventors/ Contributors Title Description Year
Debaraj Mukherjee & Anindya Goswami Indolylkojyl derivatives as inhibitor of invasion and metastasis in human mammary gland carcinomas. US Patent PCT/IN2018/050060) 2018