Malik Nishonov

Malik Nishonov

Experienced Chemist looking for New Opportunities

Location
Boulder, Colorado (Greater Denver Area)
Industry
Pharmaceuticals

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Malik Nishonov's Overview

Current
Past
  • Postdoctoral Research Associate at The University of Georgia
  • Visiting Research Scolar at University of Georgia
  • Principal Investigator, Associate Professor at Medical Institute, Osh State University/Institute Medical Problem,Kyrgyzstan Academy of Scienses
  • Ph.D. Program, Aspirant at The Institute of Chemistry of Plant Substances at the Sciences Academy of Uzbekistan
Education
  • School of Pharmacy, University of Georgia
  • Institute of Chemistry of Plant Substances at Uzbekistan Academy of Science
  • The National University of Uzbekistan, Tashkent
Connections

110 connections

Malik Nishonov's Summary

Postdoctoral and Industrial research experience in Synthetic Organic Chemistry, Chemistry of Natural Products and Medicinal Chemistry for drug discovery research,

Co-author and co-inventor of highly specific HIV integrase inhibitors and number of novel diterpenoid alkaloids and proantocianidines

Proficient in diverse areas of organic synthesis; asymmetric, chiral-pool synthesis, synthesis of heterocycles, aromatics, nucleosides, nucleotides, natural products

Specialties: Synthetic Organic Chemistry, Medicinal Chemistry and Structure Based Drug Discovery, Chemistry of Natural Products, Organometallic Chemistry

Malik Nishonov's Experience

Synthetic Organic Chemist

LC Vision LLC, Boulder CO

Pharmaceuticals industry

July 2010Present (4 years 3 months) Boulder, CO

Design and synthesis of small molecules (liquid crystal components). Application of GC, GC/MS, NMR and other laboratory equipments. Synthesis of active ingredients, intermediates for internal and external customers.
Management of research projects and maintenance of chemistry laboratories

Postdoctoral Research Associate

The University of Georgia

Educational Institution; 10,001+ employees; Higher Education industry

May 2003July 2010 (7 years 3 months)

Design and synthesis of small molecules, diverse scaffolds as potent inhibitors against HIV Integrase, HCV NS5B Polymerase, HSV, IMPDH and cancer
Analysis and interpretation of spectral data, structure activity relationship (SAR) and optimization of small molecule properties to improve therapeutic index
Collaborative research with Inhibitex, Inc. on lead optimization phase of our laboratory compounds in preclinical development. Studies of pharmacokinetics and pharmacodynamics, ADME of lead compounds

Visiting Research Scolar

University of Georgia

Educational Institution; 10,001+ employees; Higher Education industry

January 2002April 2003 (1 year 4 months)

Investigation of natural products from Encyclia longifolia, Delphinium chelianthum, Delphinium elatum "Galahad”
Chemical modification, transformation and semi-synthesis of natural products
Structure elucidation of novel natural products by application NMR (1D, 2D), IR, MS, UV and synthetic chemistry methods

Principal Investigator, Associate Professor

Medical Institute, Osh State University/Institute Medical Problem,Kyrgyzstan Academy of Scienses

July 1992December 2002 (10 years 6 months) Osh, Kyrgyzstan

Investigation of alkaloids, proantocianidines, flavonoids isolated from Polygonium, Aconitum, and Delphinium species occurring in Kyrgyzstan
Supervised the research group, Managed research projects, research laboratories
Organic Chemistry and Bioorganic Chemistry; lectures/seminars/laboratory practices

Ph.D. Program, Aspirant

The Institute of Chemistry of Plant Substances at the Sciences Academy of Uzbekistan

March 1987August 1992 (5 years 6 months) Tashkent, Uzbekistan

Investigation of alkaloids of Aconitum and Delphinium species.
Extraction, isolation, separation, purification and structure elucidation of alkaloids by using modern techniques and tools (NMR, MS, IR, UV etc.)
Chemical modification and transformation of diterpenoid alkaloids
Work on pilot production of “Allapinine”

Malik Nishonov's Patents

  • Pyridinone hydroxycyclopentyl carboxamides: hiv integrase inhibitors with therapeutic applications

    • United States Patent US 20120282218 A1
    • Issued December 7, 2010

    New chiral and achiral oxy-substituted cyclopentyl pyridinone diketocarboxamides and their derivatives and methods for their preparations are disclosed. The compounds include tautomers, regioisomers and geometric isomers. These complex carboxamides are designed as inhibitors of HIV replication through inhibition of HIV integrase. The compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents, especially other anti-HIV compounds (including other anti-HIV integrase agents), which can be used to create combination anti-HIV cocktails. Methods of treating AIDS and ARC and methods of treating or preventing infection by HIV are also described.

Malik Nishonov's Publications

  • A novel anti-HIV active integrase inhibitor with a favorable in vitro cytochrome P450 and uridine 5′-diphospho-glucuronosyltransferase metabolism profile

    • Antiviral Research Volume 98, Issue 3, June 2013, Pages 365–372
    Authors: Malik Nishonov, Sanjay Mishra, Maurice Okello, Marie K. Mankowski

    Research efforts on the human immunodeficiency virus (HIV) integrase have resulted in two approved drugs. However, co-infection of HIV with Mycobacterium tuberculosis and other microbial and viral agents has introduced added complications to this pandemic, requiring favorable drug-drug interaction profiles for antiviral therapeutics targeting HIV. Cytochrome P450 (CYP) and uridine 5′-diphospho-glucuronosyltransferase (UGT) are pivotal determining factors in the occurrence of adverse drug–drug interactions. For this reason, it is important that anti-HIV agents, such as integrase inhibitors, possess favorable profiles with respect to CYP and UGT. We have discovered a novel HIV integrase inhibitor (compound 1) that exhibits low nM antiviral activity against a diverse set of HIV-1 isolates, and against HIV-2 and the simian immunodeficiency virus (SIV). Compound 1 displays low in vitro cytotoxicity and its resistance and related drug susceptibility profiles are favorable. Data from in vitro studies revealed that compound 1 was not a substrate for UGT isoforms and that it was not an inhibitor or activator of key CYP isozymes.

  • Notable Difference in anti-HIV Activity of Integrase Inhibitors as a Consequence of Geometric and Enantiomeric Configurations

    • Bioorganic & Medicinal Chemistry Letters
    • May 23, 2013

    While some examples are known of integrase inhibitors that exhibit potent anti-HIV activity, there are very few cases reported of integrase inhibitors that show significant differences in anti-HIV activity that result from distinctions in cis- and trans-configurations as well as enantiomeric stereostructure. We describe here the design and synthesis of two enantiomeric trans-hydroxycyclopentyl carboxamides which exhibit notable difference in anti-HIV activity. This difference is explained through their binding interactions within the active site of the HIV-1 integrase intasome. The more active enantiomer 3 (EC50 25 nM) was relatively stable in human liver microsomes. Kinetic data revealed that its impact on key cytochrome P450 isozymes, as either an inhibitor or an activator, was minor, suggesting a favorable CYP profile.

  • Pro-drugs of Strand Transfer Inhibitors of HIV-1 Integrase: Inhibition Data, Structure–Activity Analysis and Anti-HIV Activity

    • Antiviral Research
    • April 1, 2010
    Authors: Malik Nishonov, Sanjay Mishra, Vasu Nair, Byung Seo, Maurice Okello
  • Discovery of a Potent HIV Integrase Inhibitor That Leads to a Prodrug with Significant anti-HIV Activity

    • ACS Med. Chem. Lett., 2011, 2 (12), pp 877–881
    • October 5, 2011
    Authors: Malik Nishonov, Sanjay Mishra, B. Seo, Vinod Uchil, Maurice Okello, Xiao-Hui Ma, Qingning Shu, Guochen Chi, Vasu Nair

    Worldwide research efforts in drug discovery involving HIV integrase have produced only one compound, raltegravir, that has been approved for clinical use in HIV/AIDS. As resistance, toxicity, and drug–drug interactions are recurring issues with all classes of anti-HIV drugs, the discovery of novel integrase inhibitors remains a significant scientific challenge. We have designed a lead HIV-1 strand transfer (ST) inhibitor (IC50 70 nM), strategically assembled on a pyridinone scaffold. A focused structure–activity investigation of this parent compound led to a significantly more potent ST inhibitor, 2 (IC50 6 ± 3 nM). Compound 2 exhibits good stability in pooled human liver microsomes. It also displays a notably favorable profile with respect to key human cytochrome P450 (CYP) isozymes and human UDP glucuronosyl transferases (UGTs). The prodrug of inhibitor 2, i.e., compound 10, was found to possess remarkable anti-HIV-1 activity in cell culture (EC50 9 ± 4 nM, CC50 135 ± 7 μM, therapeutic index = 15 000).

Malik Nishonov's Languages

  • English

    (Professional working proficiency)
  • Russian

    (Full professional proficiency)
  • Uzbek

    (Native or bilingual proficiency)
  • Kazakh

    (Professional working proficiency)
  • Kyrgyz

    (Native or bilingual proficiency)

Malik Nishonov's Skills & Expertise

  1. Organic Synthesis
  2. Data Interpretation
  3. Team Leadership
  4. Experimentation
  5. Teamwork
  6. Medicinal Chemistry
  7. Drug Discovery
  8. NMR
  9. Organic Chemistry
  10. HPLC
  11. Purification
  12. Chemistry
  13. Lifesciences
  14. Characterization
  15. Organometallic Chemistry

Malik Nishonov's Education

School of Pharmacy, University of Georgia

Postdoctoral Fellow, Synthetic and Medicinal Chemistry

20032010

Design and Synthesis of small molecules targeting HIV, HCV, HSV, IMPDH, and cancer

Activities and Societies: American Chemical Society,

Institute of Chemistry of Plant Substances at Uzbekistan Academy of Science

Aspirant, Ph.D. in Chemistry, Bioorganic and Medicinal Chemistry

19871990

Grade: A

Investigation of natural products- alkaloids,proantocianidinas, coumarins, flavonoids, carbohydrates to drug discovery

Activities and Societies: Council of Young Scientists at Academy of Sciences of Uzbekistan, Prizewinner Council of Young Scientists 1988, 1990, The Mendeleev Chemical Society

The National University of Uzbekistan, Tashkent

Bachelor of Science (B.Sc.), Chemistry

19791984

Grade: A+

Hydrodynamic properties of the copolymer of vinyl ether of lupinine with N-vinylpyrrolidone

Activities and Societies: Chemistry Club at the University, The Mendeleev Chemical Society

Malik Nishonov's Additional Information

Interests:

Sciences: Drug Discovery Research, miRNAs, Synthetic Chemistry, Natural Products Chemistry, Structure-Activity Relationships, Medicinal Chemistry, Bioengineering, Microbiology Sport: Tennis, Soccer, Camping, Travel, Swimming

Groups and Associations:

American Chemical Society, New York Academy of Sciences, The Mendeleev Chemical Society Biotech & Pharma Professionals Network Georgia Bio's Emerging Leaders Network Pharmaceutical Discussion Group

Malik Nishonov's Volunteer Experience & Causes

  • Volunteer Experience

    • Science activity

      Mesa Elementary
      • Children

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