Muzafar Ahmad Rather

University of Minnesota System

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Zahoor Ahmad

Barrow Neurological Institute

Zubair Shanib Bhat

Indian Institute of Integrative Medicine

Showkeen Muzamil Bashir

Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir

Mubashir Maqbool

Indian Institute of Integrative Medicine

Showkat Ul Nabi

Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir

Aabid Manzoor Shah

University of Sargodha

Sofi Imtiyaz Ali

Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir

Aehtesham Hussain

National Centre for Cell Science

Qazi Parvaiz Hassan

Indian Institute of Integrative Medicine

Wajid Mohammad Sheikh

Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir

Cooperative Institutions

Indian Institute of Integrative Medicine

University of Kashmir

Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir

Council of Scientific and Industrial Research

Academy of Scientific and Innovative Research

Veterinary & Animal Husbandry

Cluster University Srinagar

University of Jammu

Sher-i-Kashmir Institute of Medical Sciences

King Saud University

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Design and synthesis of indolopyridone hybrids as new antituberculosis agents

Microbial Pathogenesis (2017)

Muzafar Ahmad Rather Faheem Rasool Zubair Shanib Bhat Hafiz-Ullah Dar Mubashir Maqbool

10.1016/j.micpath.2017.10.045

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Citations (7)

In vitro antimycobacterial activity of 2-(((2-hydroxyphenyl)amino)methylene)-5,5-dimethylcyclohexane-1,3-dione: A new chemical entity against Mycobacterium tuberculosis

International Journal of Infectious Diseases (2018)

Muzafar Ahmad Rather Zubair Shanib Bhat Ali Mohd Lone Shajrul Amin Bilal A. Bhat

Background: In our on-going efforts towards tuberculosis (TB) drug discovery programme, a high-throughput whole cell-based phenotypic screening of thousands of compounds against Mycobacterium tuberculosis H37Rv lead to the identification of a lead compound; 2-(((2-hydroxyphenyl)amino)methylene)-5,5-dimethylcyclohexane-1,3-dione (PAMCHD). In our earlier studies, it was observed that the test compound exhibited antimicrobial activity that was restricted to M. tuberculosis only. The test compound also proved to be non-toxic against a panel of human cell lines. Therefore, the present study was planned with an aim to further explore the antimycobacterial potential of the PAMCHD against M. tuberculosis H37Rv. Methods & Materials: In this study, we determined the minimum inhibitory concentration (MIC) and Minimum bactericidal concentration (MBC) of the PAMCHD. Kill curve and drug interaction studies were performed. Effect of serum/protein binding on PAMCHD activity was explored. Further, post antibiotic effect (PAE), Mutation frequency (MF) and mutant prevention concentration (MPC) were studied. Results: PAMCHD proved to be tuberculostatic (MIC, 2.5 μg/mL) as well as tuberculocidal (MBC, 5.0 μg/mL) agent. This compound was equipotent against drug resistant M. tuberculosis clinical isolates (MIC, 2.5-10 μg/mL). The dynamics of M. tuberculosis killing revealed its time as well as concentration-dependent anti-TB activity with an Emax of 10.0 μg/mL (at this concentration M.tuberculosis culture were completely sterilized). PAMCHD acts synergistically and additively with key first line and second line ATDs respectively. PAE of PAMCHD's was found to be 63.1 and 103.8 h at 4x and 8x MIC and that of INH (used as a control ATD) were 39.8 and 127.9 h respectively. MF for M. tuberculosis against PAMCHD was lower than that of INH at all the tested concentrations. The capacity of preventing emergence of resistant mutants of PAMCHD was found to be comparable to rifampin (RIF) as mutant MPC of both was observed to be 160 μg/mL. MPC/MIC value of PAMCHD (i.e. 64) matched to the best-known value among ATDs (i.e. 68) exhibited by moxifloxacin reflecting its additional significant potential to prevent emergence of resistant mutants. Conclusion: PAMCHD bears significant antituberculosis potential proven at various levels that warrant its further evaluation towards TB drug development.

Antimycobacterial

Minimum bactericidal concentration

10.1016/j.ijid.2018.04.3656

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In vitro potency of 2-(((2-hydroxyphenyl)amino)methylene)-5,5-dimethylcyclohexane-1,3-dione against drug-resistant and non-replicating persisters of Mycobacterium tuberculosis

Journal of Global Antimicrobial Resistance (2021)

Muzafar Ahmad Rather Zubair Shanib Bhat Ali Mohd Lone Mubashir Maqbool Bilal A. Bhat

New antituberculosis agents active against drug-resistant and non-replicating tubercle bacilli are required. We evaluated a previously identified hit, 2-(((2-hydroxyphenyl)amino)methylene)-5,5-dimethylcyclohexane-1,3-dione (PAMCHD), against several clinical Mycobacterium tuberculosis isolates, including multidrug-resistant (MDR) strains and non-replicating drug-tolerant persisters of M. tuberculosis H37Rv.PAMCHD's potential against drug-resistant M. tuberculosis was investigated by broth microdilution. CFU enumeration was performed to determine PAMCHD's activity against five types of dormant bacilli.No significant differences in MICs of PAMCHD were observed against M. tuberculosis H37Rv (2.5-5 µg/mL) and eight drug-susceptible strains (1.25-5 µg/mL) as well as drug-resistant strains including six isoniazid (INH)-resistant (2.5-10 µg/mL), one INH + ethambutol (EMB)-resistant (5 µg/mL), one rifampicin (RIF) + EMB-resistant (5 µg/mL) and three MDR (2.5-10 µg/mL) strains. Thus, PAMCHD maintains activity against all kinds of clinical strains, especially MDR. Regarding drug-tolerant persisters, INH and RIF killed, respectively, 0.5 and 5.0 log10 CFU of non-replicating persisters developed by hypoxia and 1.5 and 2.5 log10 CFU developed by nutrient starvation at 64 × of their respective MIC against actively dividing cultures. In contrast, PAMCHD sterilised persister cultures developed by hypoxia (killed 6.5 log10 CFU) or starvation (killed 7.5 log10 CFU). PAMCHD sterilised RIF-tolerant (tolerance level up to 100 µg/mL of RIF) 100-day-old static persisters at 64 × MIC, while moxifloxacin killed only 1.0 log10 CFU of these persisters at 64 × MIC.PAMCHD offers significant potential against MDR-TB and exhibits notable potency against non-replicating drug-tolerant M. tuberculosis persisters. These findings warrant further studies of PAMCHD for further anti-TB drug development.

Multidrug tolerance

Broth microdilution

10.1016/j.jgar.2021.03.015

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Antimicrobial investigation of selected soil actinomycetes isolated from unexplored regions of Kashmir Himalayas, India

Microbial Pathogenesis (2017)

Aabid Manzoor Shah Shakeel-u-Rehman Aehtesham Hussain Saleem Mushtaq Muzafar Ahmad Rather

Strain (injury)

10.1016/j.micpath.2017.06.017

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Drug targets exploited in Mycobacterium tuberculosis: Pitfalls and promises on the horizon

Biomedicine & Pharmacotherapy (2018)

Zubair Shanib Bhat Muzafar Ahmad Rather Mubashir Maqbool Zahoor Ahmad

Pandemic

10.1016/j.biopha.2018.04.176

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Discovery of anti-microbial and anti-tubercular molecules from Fusarium solani : an endophyte of Glycyrrhiza glabra

Journal of Applied Microbiology (2017)

Aabid Manzoor Shah Muzafar Ahmad Rather Qazi Parvaiz Hassan Mushtaq A. Aga Saleem Mushtaq

Glycyrrhiza glabra is a high-value medicinal plant thriving in biodiversity rich Kashmir Himalaya. The present study was designed to explore the fungal endophytes from G. glabra as a source of bioactive molecules.The extracts prepared from the isolated endophytes were evaluated for anti-microbial activities using broth micro-dilution assay. The endophytic strain coded as A2 exhibiting promising anti-bacterial as well as anti-tuberculosis activity was identified as Fusarium solani by ITS-5.8S ribosomal gene sequencing technique. This strain was subjected to large-scale fermentation followed by isolation of its bioactive compounds using column chromatography. From the results of spectral data analysis and comparison with literature, the molecules were identified as 3,6,9-trihydroxy-7-methoxy-4,4-dimethyl-3,4-dihydro-1H-benzo[g]isochromene-5,10-dione (1), fusarubin (2), 3-O-methylfusarubin (3) and javanicin (4). Compound 1 is reported for the first time from this strain. All the four compounds inhibited the growth of various tested bacterial strains with MIC values in the range of <1 to 256 μg ml-1 . Fusarubin showed good activity against Mycobacterium tuberculosis strain H37Rv with MIC value of 8 μg ml-1 , whereas compounds 1, 3 and 4 exhibited moderate activity with MIC values of 256, 64, 32 μg ml-1 , respectively.To the best of our knowledge, this is the first study that reports significant anti-tuberculosis potential of bioactive molecules from endophytic F. solani evaluated against the virulent strain of M. tuberculosis. This study sets background towards their synthetic intervention for activity enhancement experiments in anti-microbial drug discovery programme.Due to the chemoprofile variation of same endophyte with respect to source plant and ecoregions, further studies are required to explore endophytes of medicinal plants of all unusual biodiversity rich ecoregions for important and or novel bioactive molecules.

Fusarium solani

Glycyrrhiza

Strain (injury)

Endophyte

10.1111/jam.13410

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Citations (48)

Healing the Wound

Dialogue A Journal of Mormon Thought (2024)

Muzafar Ahmad Rather

The Good Doctor Muses,Will You be bound?And I Remember,Surgeons ask and tapmy swollen shin and splinter the skin to leechout the infection. The leather straps snapin calloused hands while others reachinto cowhide and pigskin bags. Their fingerspull out glass whisky jars and worn scalpels.They place them lovingly on the pine dresser,line the bright metal tools on the woolthe blanket mother spread to protect the wood.When the surgeons begin to pourThe whiskey I said,Not a drop of Satan's blood,No whiskey, not one particle. No stupor.I will feel every second of that blade.I will know every layer of flesh you raise.

10.5406/15549399.57.1.15

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Review of: "Antimicrobial Sensitivity of Plant Extracts of Acacia arabica, Prosopis juliflora, Abutilon indicum, and Bryonia laciniosa on Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli"

Muzafar Ahmad Rather

10.32388/k78qhs

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An update on emerging therapeutics to combat COVID‐19

Basic & Clinical Pharmacology & Toxicology (2021)

Naveed Nazir Shah Showkat Ul Nabi Muzafar Ahmad Rather Qudratullah Kalwar Sofi Imtiyaz Ali

Abstract Background The COVID‐19 pandemic has demanded effective therapeutic protocol from researchers and clinicians across the world. Currently, a large amount of primary data have been generated from several preclinical studies. At least 300 clinical trials are underway for drug repurposing against COVID‐19; the clinician needs objective evidence‐based medication to treat COVID‐19. Observations Single‐stranded RNA viral genome of SARS‐CoV‐2 encodes structural proteins (spike protein), non‐structural enzymatic proteins (RNA‐dependent RNA polymerase, helicase, papain‐like protease, 3‐chymotrypsin‐like protease) and other accessory proteins. These four enzymatic proteins on spike protein are rate‐limiting steps in viral replications and, therefore, an attractive target for drug development against SARS‐CoV‐2. In silico and in vitro studies have identified various potential epitomes as candidate sequences for vaccine development. These studies have also revealed potential targets for drug development and drug repurposing against COVID‐19. Clinical trials utilizing antiviral drugs and other drugs have given inconclusive results regarding their clinical efficacy and side effects. The need for angiotensin‐converting enzyme (ACE‐2) inhibitors/angiotensin receptor blockers and corticosteroids has been recommended. Western countries have adopted telemedicine as an alternative to prevent transmission of infection in the population. Currently, no proven, evidence‐based therapeutic regimen exists for COVID‐19. Conclusion The COVID‐19 pandemic has put tremendous pressure on researchers to evaluate and approve drugs effective against the disease. Well‐controlled randomized trials should assess medicines that are not marketed with substantial evidence of safety and efficacy and more emphasis on time tested approaches for drug evaluation.

2019-20 coronavirus outbreak

Pandemic

Coronavirus Infections

Betacoronavirus

10.1111/bcpt.13600

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Citations (11)

Antituberculotic activity of actinobacteria isolated from the rare habitats

Letters in Applied Microbiology (2017)

Aehtesham Hussain Muzafar Ahmad Rather Aabid Manzoor Shah Zubair Shanib Bhat Aabid Manzoor Shah

A distinctive screening procedure resulted in the isolation and identification of antituberculotic actinobacteria. In this course, a total of 125 actinobacteria were isolated from various soil samples from untapped areas in Northwestern Himalayas, India. The antibacterial screening showed that 26 isolates inhibited the growth of at least one of the tested bacterial pathogens including Staphylococcus aureus (ATCC 25923), Staphylococcus epidermidis (ATCC 12228), Bacillus subtilis (ATCC 11774), Micrococcus luteus (ATCC 10240), Escherichia coli (10536), Pseudomonas aeruginosa (ATCC 10145) and Klebsiella pneumonia (ATCC BAA-2146). The production media was optimized for the active strains by estimation of their extract value by the quantification of the ethyl acetate extract. The screening of fermentation products from the selected 26 bioactive isolates revealed that 10 strains have metabolites antagonistic against the standard H37Rv strain of Mycobacterium tuberculosis. The characterization by 16S rRNA gene sequencing and phylogenetic analysis demonstrated the diverse nature of these antituberculosis strains. The secondary metabolites of potent, rare strain, Lentzea violacea AS08 exhibited promising antituberculosis activity with minimal inhibitory concentration (MIC) of 3·9 μg ml-1 . The metabolites identified by gas chromatography-mass spectrometry (GC-MS) included, Phenol, 2,5-bis (1, 1-dimethylethyl), n-Hexadecanoic acid, Hexadecanoic acid methyl-ester, Hexadecanoic acid ethyl-ester and, 9,12-Octadecadienoyl chloride(Z,Z) are biologically significant molecules.The study presents the isolation of rare actinobacteria from untapped sites in the Northwestern Himalayas and their in vitro potential against Mycobacterium tuberculosis for their metabolites. The study revealed that exploring the untapped natural sources as one of the resourceful approaches for the discovery of new natural products. This study also provided strong evidence for the ability of rare and potent actinobacterial strains to produce bioactive compounds with antagonistic activity and these metabolites can be studied for inhibitory potential.

Micrococcus luteus

10.1111/lam.12773

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Citations (16)